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Gene therapy – Wikipedia

In the medicine field, gene therapy (also called human gene transfer) is the therapeutic delivery of nucleic acid into a patient’s cells as a drug to treat disease.[1][2] The first attempt at modifying human DNA was performed in 1980 by Martin Cline, but the first successful nuclear gene transfer in humans, approved by the National Institutes of Health, was performed in May 1989.[3] The first therapeutic use of gene transfer as well as the first direct insertion of human DNA into the nuclear genome was performed by French Anderson in a trial starting in September 1990.

Between 1989 and February 2016, over 2,300 clinical trials had been conducted, more than half of them in phase I.[4]

Not all medical procedures that introduce alterations to a patient’s genetic makeup can be considered gene therapy. Bone marrow transplantation and organ transplants in general have been found to introduce foreign DNA into patients.[5] Gene therapy is defined by the precision of the procedure and the intention of direct therapeutic effects.

Gene therapy was conceptualized in 1972, by authors who urged caution before commencing human gene therapy studies.

The first attempt, an unsuccessful one, at gene therapy (as well as the first case of medical transfer of foreign genes into humans not counting organ transplantation) was performed by Martin Cline on 10 July 1980.[6][7] Cline claimed that one of the genes in his patients was active six months later, though he never published this data or had it verified[8] and even if he is correct, it’s unlikely it produced any significant beneficial effects treating beta-thalassemia.

After extensive research on animals throughout the 1980s and a 1989 bacterial gene tagging trial on humans, the first gene therapy widely accepted as a success was demonstrated in a trial that started on 14 September 1990, when Ashi DeSilva was treated for ADA-SCID.[9]

The first somatic treatment that produced a permanent genetic change was performed in 1993.[citation needed]

Gene therapy is a way to fix a genetic problem at its source. The polymers are either translated into proteins, interfere with target gene expression, or possibly correct genetic mutations.

The most common form uses DNA that encodes a functional, therapeutic gene to replace a mutated gene. The polymer molecule is packaged within a “vector”, which carries the molecule inside cells.

Early clinical failures led to dismissals of gene therapy. Clinical successes since 2006 regained researchers’ attention, although as of 2014, it was still largely an experimental technique.[10] These include treatment of retinal diseases Leber’s congenital amaurosis[11][12][13][14] and choroideremia,[15] X-linked SCID,[16] ADA-SCID,[17][18] adrenoleukodystrophy,[19] chronic lymphocytic leukemia (CLL),[20] acute lymphocytic leukemia (ALL),[21] multiple myeloma,[22] haemophilia,[18] and Parkinson’s disease.[23] Between 2013 and April 2014, US companies invested over $600 million in the field.[24]

The first commercial gene therapy, Gendicine, was approved in China in 2003 for the treatment of certain cancers.[25] In 2011 Neovasculgen was registered in Russia as the first-in-class gene-therapy drug for treatment of peripheral artery disease, including critical limb ischemia.[26]In 2012 Glybera, a treatment for a rare inherited disorder, became the first treatment to be approved for clinical use in either Europe or the United States after its endorsement by the European Commission.[10][27]

Following early advances in genetic engineering of bacteria, cells, and small animals, scientists started considering how to apply it to medicine. Two main approaches were considered replacing or disrupting defective genes.[28] Scientists focused on diseases caused by single-gene defects, such as cystic fibrosis, haemophilia, muscular dystrophy, thalassemia, and sickle cell anemia. Glybera treats one such disease, caused by a defect in lipoprotein lipase.[27]

DNA must be administered, reach the damaged cells, enter the cell and either express or disrupt a protein.[29] Multiple delivery techniques have been explored. The initial approach incorporated DNA into an engineered virus to deliver the DNA into a chromosome.[30][31] Naked DNA approaches have also been explored, especially in the context of vaccine development.[32]

Generally, efforts focused on administering a gene that causes a needed protein to be expressed. More recently, increased understanding of nuclease function has led to more direct DNA editing, using techniques such as zinc finger nucleases and CRISPR. The vector incorporates genes into chromosomes. The expressed nucleases then knock out and replace genes in the chromosome. As of 2014 these approaches involve removing cells from patients, editing a chromosome and returning the transformed cells to patients.[33]

Gene editing is a potential approach to alter the human genome to treat genetic diseases,[34] viral diseases,[35] and cancer.[36] As of 2016 these approaches were still years from being medicine.[37][38]

Gene therapy may be classified into two types:

In somatic cell gene therapy (SCGT), the therapeutic genes are transferred into any cell other than a gamete, germ cell, gametocyte, or undifferentiated stem cell. Any such modifications affect the individual patient only, and are not inherited by offspring. Somatic gene therapy represents mainstream basic and clinical research, in which therapeutic DNA (either integrated in the genome or as an external episome or plasmid) is used to treat disease.

Over 600 clinical trials utilizing SCGT are underway in the US. Most focus on severe genetic disorders, including immunodeficiencies, haemophilia, thalassaemia, and cystic fibrosis. Such single gene disorders are good candidates for somatic cell therapy. The complete correction of a genetic disorder or the replacement of multiple genes is not yet possible. Only a few of the trials are in the advanced stages.[39]

In germline gene therapy (GGT), germ cells (sperm or egg cells) are modified by the introduction of functional genes into their genomes. Modifying a germ cell causes all the organism’s cells to contain the modified gene. The change is therefore heritable and passed on to later generations. Australia, Canada, Germany, Israel, Switzerland, and the Netherlands[40] prohibit GGT for application in human beings, for technical and ethical reasons, including insufficient knowledge about possible risks to future generations[40] and higher risks versus SCGT.[41] The US has no federal controls specifically addressing human genetic modification (beyond FDA regulations for therapies in general).[40][42][43][44]

The delivery of DNA into cells can be accomplished by multiple methods. The two major classes are recombinant viruses (sometimes called biological nanoparticles or viral vectors) and naked DNA or DNA complexes (non-viral methods).

In order to replicate, viruses introduce their genetic material into the host cell, tricking the host’s cellular machinery into using it as blueprints for viral proteins. Retroviruses go a stage further by having their genetic material copied into the genome of the host cell. Scientists exploit this by substituting a virus’s genetic material with therapeutic DNA. (The term ‘DNA’ may be an oversimplification, as some viruses contain RNA, and gene therapy could take this form as well.) A number of viruses have been used for human gene therapy, including retroviruses, adenoviruses, herpes simplex, vaccinia, and adeno-associated virus.[4] Like the genetic material (DNA or RNA) in viruses, therapeutic DNA can be designed to simply serve as a temporary blueprint that is degraded naturally or (at least theoretically) to enter the host’s genome, becoming a permanent part of the host’s DNA in infected cells.

Non-viral methods present certain advantages over viral methods, such as large scale production and low host immunogenicity. However, non-viral methods initially produced lower levels of transfection and gene expression, and thus lower therapeutic efficacy. Later technology remedied this deficiency.[citation needed]

Methods for non-viral gene therapy include the injection of naked DNA, electroporation, the gene gun, sonoporation, magnetofection, the use of oligonucleotides, lipoplexes, dendrimers, and inorganic nanoparticles.

Some of the unsolved problems include:

Three patients’ deaths have been reported in gene therapy trials, putting the field under close scrutiny. The first was that of Jesse Gelsinger in 1999. Jesse Gelsinger died because of immune rejection response.[51] One X-SCID patient died of leukemia in 2003.[9] In 2007, a rheumatoid arthritis patient died from an infection; the subsequent investigation concluded that the death was not related to gene therapy.[52]

In 1972 Friedmann and Roblin authored a paper in Science titled “Gene therapy for human genetic disease?”[53] Rogers (1970) was cited for proposing that exogenous good DNA be used to replace the defective DNA in those who suffer from genetic defects.[54]

In 1984 a retrovirus vector system was designed that could efficiently insert foreign genes into mammalian chromosomes.[55]

The first approved gene therapy clinical research in the US took place on 14 September 1990, at the National Institutes of Health (NIH), under the direction of William French Anderson.[56] Four-year-old Ashanti DeSilva received treatment for a genetic defect that left her with ADA-SCID, a severe immune system deficiency. The defective gene of the patient’s blood cells was replaced by the functional variant. Ashantis immune system was partially restored by the therapy. Production of the missing enzyme was temporarily stimulated, but the new cells with functional genes were not generated. She led a normal life only with the regular injections performed every two months. The effects were successful, but temporary.[57]

Cancer gene therapy was introduced in 1992/93 (Trojan et al. 1993).[58] The treatment of glioblastoma multiforme, the malignant brain tumor whose outcome is always fatal, was done using a vector expressing antisense IGF-I RNA (clinical trial approved by NIH protocolno.1602 November 24, 1993,[59] and by the FDA in 1994). This therapy also represents the beginning of cancer immunogene therapy, a treatment which proves to be effective due to the anti-tumor mechanism of IGF-I antisense, which is related to strong immune and apoptotic phenomena.

In 1992 Claudio Bordignon, working at the Vita-Salute San Raffaele University, performed the first gene therapy procedure using hematopoietic stem cells as vectors to deliver genes intended to correct hereditary diseases.[60] In 2002 this work led to the publication of the first successful gene therapy treatment for adenosine deaminase deficiency (ADA-SCID). The success of a multi-center trial for treating children with SCID (severe combined immune deficiency or “bubble boy” disease) from 2000 and 2002, was questioned when two of the ten children treated at the trial’s Paris center developed a leukemia-like condition. Clinical trials were halted temporarily in 2002, but resumed after regulatory review of the protocol in the US, the United Kingdom, France, Italy, and Germany.[61]

In 1993 Andrew Gobea was born with SCID following prenatal genetic screening. Blood was removed from his mother’s placenta and umbilical cord immediately after birth, to acquire stem cells. The allele that codes for adenosine deaminase (ADA) was obtained and inserted into a retrovirus. Retroviruses and stem cells were mixed, after which the viruses inserted the gene into the stem cell chromosomes. Stem cells containing the working ADA gene were injected into Andrew’s blood. Injections of the ADA enzyme were also given weekly. For four years T cells (white blood cells), produced by stem cells, made ADA enzymes using the ADA gene. After four years more treatment was needed.[62]

Jesse Gelsinger’s death in 1999 impeded gene therapy research in the US.[63][64] As a result, the FDA suspended several clinical trials pending the reevaluation of ethical and procedural practices.[65]

The modified cancer gene therapy strategy of antisense IGF-I RNA (NIH n 1602)[59] using antisense / triple helix anti-IGF-I approach was registered in 2002 by Wiley gene therapy clinical trial – n 635 and 636. The approach has shown promising results in the treatment of six different malignant tumors: glioblastoma, cancers of liver, colon, prostate, uterus, and ovary (Collaborative NATO Science Programme on Gene Therapy USA, France, Poland n LST 980517 conducted by J. Trojan) (Trojan et al., 2012). This anti-gene antisense/triple helix therapy has proven to be efficient, due to the mechanism stopping simultaneously IGF-I expression on translation and transcription levels, strengthening anti-tumor immune and apoptotic phenomena.

Sickle-cell disease can be treated in mice.[66] The mice which have essentially the same defect that causes human cases used a viral vector to induce production of fetal hemoglobin (HbF), which normally ceases to be produced shortly after birth. In humans, the use of hydroxyurea to stimulate the production of HbF temporarily alleviates sickle cell symptoms. The researchers demonstrated this treatment to be a more permanent means to increase therapeutic HbF production.[67]

A new gene therapy approach repaired errors in messenger RNA derived from defective genes. This technique has the potential to treat thalassaemia, cystic fibrosis and some cancers.[68]

Researchers created liposomes 25 nanometers across that can carry therapeutic DNA through pores in the nuclear membrane.[69]

In 2003 a research team inserted genes into the brain for the first time. They used liposomes coated in a polymer called polyethylene glycol, which unlike viral vectors, are small enough to cross the bloodbrain barrier.[70]

Short pieces of double-stranded RNA (short, interfering RNAs or siRNAs) are used by cells to degrade RNA of a particular sequence. If a siRNA is designed to match the RNA copied from a faulty gene, then the abnormal protein product of that gene will not be produced.[71]

Gendicine is a cancer gene therapy that delivers the tumor suppressor gene p53 using an engineered adenovirus. In 2003, it was approved in China for the treatment of head and neck squamous cell carcinoma.[25]

In March researchers announced the successful use of gene therapy to treat two adult patients for X-linked chronic granulomatous disease, a disease which affects myeloid cells and damages the immune system. The study is the first to show that gene therapy can treat the myeloid system.[72]

In May a team reported a way to prevent the immune system from rejecting a newly delivered gene.[73] Similar to organ transplantation, gene therapy has been plagued by this problem. The immune system normally recognizes the new gene as foreign and rejects the cells carrying it. The research utilized a newly uncovered network of genes regulated by molecules known as microRNAs. This natural function selectively obscured their therapeutic gene in immune system cells and protected it from discovery. Mice infected with the gene containing an immune-cell microRNA target sequence did not reject the gene.

In August scientists successfully treated metastatic melanoma in two patients using killer T cells genetically retargeted to attack the cancer cells.[74]

In November researchers reported on the use of VRX496, a gene-based immunotherapy for the treatment of HIV that uses a lentiviral vector to deliver an antisense gene against the HIV envelope. In a phase I clinical trial, five subjects with chronic HIV infection who had failed to respond to at least two antiretroviral regimens were treated. A single intravenous infusion of autologous CD4 T cells genetically modified with VRX496 was well tolerated. All patients had stable or decreased viral load; four of the five patients had stable or increased CD4 T cell counts. All five patients had stable or increased immune response to HIV antigens and other pathogens. This was the first evaluation of a lentiviral vector administered in a US human clinical trial.[75][76]

In May researchers announced the first gene therapy trial for inherited retinal disease. The first operation was carried out on a 23-year-old British male, Robert Johnson, in early 2007.[77]

Leber’s congenital amaurosis is an inherited blinding disease caused by mutations in the RPE65 gene. The results of a small clinical trial in children were published in April.[11] Delivery of recombinant adeno-associated virus (AAV) carrying RPE65 yielded positive results. In May two more groups reported positive results in independent clinical trials using gene therapy to treat the condition. In all three clinical trials, patients recovered functional vision without apparent side-effects.[11][12][13][14]

In September researchers were able to give trichromatic vision to squirrel monkeys.[78] In November 2009, researchers halted a fatal genetic disorder called adrenoleukodystrophy in two children using a lentivirus vector to deliver a functioning version of ABCD1, the gene that is mutated in the disorder.[79]

An April paper reported that gene therapy addressed achromatopsia (color blindness) in dogs by targeting cone photoreceptors. Cone function and day vision were restored for at least 33 months in two young specimens. The therapy was less efficient for older dogs.[80]

In September it was announced that an 18-year-old male patient in France with beta-thalassemia major had been successfully treated.[81] Beta-thalassemia major is an inherited blood disease in which beta haemoglobin is missing and patients are dependent on regular lifelong blood transfusions.[82] The technique used a lentiviral vector to transduce the human -globin gene into purified blood and marrow cells obtained from the patient in June 2007.[83] The patient’s haemoglobin levels were stable at 9 to 10 g/dL. About a third of the hemoglobin contained the form introduced by the viral vector and blood transfusions were not needed.[83][84] Further clinical trials were planned.[85] Bone marrow transplants are the only cure for thalassemia, but 75% of patients do not find a matching donor.[84]

Cancer immunogene therapy using modified antigene, antisense/triple helix approach was introduced in South America in 2010/11 in La Sabana University, Bogota (Ethical Committee 14 December 2010, no P-004-10). Considering the ethical aspect of gene diagnostic and gene therapy targeting IGF-I, the IGF-I expressing tumors i.e. lung and epidermis cancers were treated (Trojan et al. 2016).[86][87]

In 2007 and 2008, a man (Timothy Ray Brown) was cured of HIV by repeated hematopoietic stem cell transplantation (see also allogeneic stem cell transplantation, allogeneic bone marrow transplantation, allotransplantation) with double-delta-32 mutation which disables the CCR5 receptor. This cure was accepted by the medical community in 2011.[88] It required complete ablation of existing bone marrow, which is very debilitating.

In August two of three subjects of a pilot study were confirmed to have been cured from chronic lymphocytic leukemia (CLL). The therapy used genetically modified T cells to attack cells that expressed the CD19 protein to fight the disease.[20] In 2013, the researchers announced that 26 of 59 patients had achieved complete remission and the original patient had remained tumor-free.[89]

Human HGF plasmid DNA therapy of cardiomyocytes is being examined as a potential treatment for coronary artery disease as well as treatment for the damage that occurs to the heart after myocardial infarction.[90][91]

In 2011 Neovasculgen was registered in Russia as the first-in-class gene-therapy drug for treatment of peripheral artery disease, including critical limb ischemia; it delivers the gene encoding for VEGF.[92][26] Neovasculogen is a plasmid encoding the CMV promoter and the 165 amino acid form of VEGF.[93][94]

The FDA approved Phase 1 clinical trials on thalassemia major patients in the US for 10 participants in July.[95] The study was expected to continue until 2015.[85]

In July 2012, the European Medicines Agency recommended approval of a gene therapy treatment for the first time in either Europe or the United States. The treatment used Alipogene tiparvovec (Glybera) to compensate for lipoprotein lipase deficiency, which can cause severe pancreatitis.[96] The recommendation was endorsed by the European Commission in November 2012[10][27][97][98] and commercial rollout began in late 2014.[99] Alipogene tiparvovec was expected to cost around $1.6 million per treatment in 2012,[100] revised to $1 million in 2015,[101] making it the most expensive medicine in the world at the time.[102] As of 2016, only one person had been treated with drug.[103]

In December 2012, it was reported that 10 of 13 patients with multiple myeloma were in remission “or very close to it” three months after being injected with a treatment involving genetically engineered T cells to target proteins NY-ESO-1 and LAGE-1, which exist only on cancerous myeloma cells.[22]

In March researchers reported that three of five adult subjects who had acute lymphocytic leukemia (ALL) had been in remission for five months to two years after being treated with genetically modified T cells which attacked cells with CD19 genes on their surface, i.e. all B-cells, cancerous or not. The researchers believed that the patients’ immune systems would make normal T-cells and B-cells after a couple of months. They were also given bone marrow. One patient relapsed and died and one died of a blood clot unrelated to the disease.[21]

Following encouraging Phase 1 trials, in April, researchers announced they were starting Phase 2 clinical trials (called CUPID2 and SERCA-LVAD) on 250 patients[104] at several hospitals to combat heart disease. The therapy was designed to increase the levels of SERCA2, a protein in heart muscles, improving muscle function.[105] The FDA granted this a Breakthrough Therapy Designation to accelerate the trial and approval process.[106] In 2016 it was reported that no improvement was found from the CUPID 2 trial.[107]

In July researchers reported promising results for six children with two severe hereditary diseases had been treated with a partially deactivated lentivirus to replace a faulty gene and after 732 months. Three of the children had metachromatic leukodystrophy, which causes children to lose cognitive and motor skills.[108] The other children had Wiskott-Aldrich syndrome, which leaves them to open to infection, autoimmune diseases, and cancer.[109] Follow up trials with gene therapy on another six children with Wiskott-Aldrich syndrome were also reported as promising.[110][111]

In October researchers reported that two children born with adenosine deaminase severe combined immunodeficiency disease (ADA-SCID) had been treated with genetically engineered stem cells 18 months previously and that their immune systems were showing signs of full recovery. Another three children were making progress.[18] In 2014 a further 18 children with ADA-SCID were cured by gene therapy.[112] ADA-SCID children have no functioning immune system and are sometimes known as “bubble children.”[18]

Also in October researchers reported that they had treated six hemophilia sufferers in early 2011 using an adeno-associated virus. Over two years later all six were producing clotting factor.[18][113]

In January researchers reported that six choroideremia patients had been treated with adeno-associated virus with a copy of REP1. Over a six-month to two-year period all had improved their sight.[114][115] By 2016, 32 patients had been treated with positive results and researchers were hopeful the treatment would be long-lasting.[15] Choroideremia is an inherited genetic eye disease with no approved treatment, leading to loss of sight.

In March researchers reported that 12 HIV patients had been treated since 2009 in a trial with a genetically engineered virus with a rare mutation (CCR5 deficiency) known to protect against HIV with promising results.[116][117]

Clinical trials of gene therapy for sickle cell disease were started in 2014.[118][119] There is a need for high quality randomised controlled trials assessing the risks and benefits involved with gene therapy for people with sickle cell disease.[120]

In February LentiGlobin BB305, a gene therapy treatment undergoing clinical trials for treatment of beta thalassemia gained FDA “breakthrough” status after several patients were able to forgo the frequent blood transfusions usually required to treat the disease.[121]

In March researchers delivered a recombinant gene encoding a broadly neutralizing antibody into monkeys infected with simian HIV; the monkeys’ cells produced the antibody, which cleared them of HIV. The technique is named immunoprophylaxis by gene transfer (IGT). Animal tests for antibodies to ebola, malaria, influenza, and hepatitis were underway.[122][123]

In March, scientists, including an inventor of CRISPR, Jennifer Doudna, urged a worldwide moratorium on germline gene therapy, writing “scientists should avoid even attempting, in lax jurisdictions, germline genome modification for clinical application in humans” until the full implications “are discussed among scientific and governmental organizations”.[124][125][126][127]

In October, researchers announced that they had treated a baby girl, Layla Richards, with an experimental treatment using donor T-cells genetically engineered using TALEN to attack cancer cells. One year after the treatment she was still free of her cancer (a highly aggressive form of acute lymphoblastic leukaemia [ALL]).[128] Children with highly aggressive ALL normally have a very poor prognosis and Layla’s disease had been regarded as terminal before the treatment.[129]

In December, scientists of major world academies called for a moratorium on inheritable human genome edits, including those related to CRISPR-Cas9 technologies[130] but that basic research including embryo gene editing should continue.[131]

In April the Committee for Medicinal Products for Human Use of the European Medicines Agency endorsed a gene therapy treatment called Strimvelis[132][133] and the European Commission approved it in June.[134] This treats children born with adenosine deaminase deficiency and who have no functioning immune system. This was the second gene therapy treatment to be approved in Europe.[135]

In October, Chinese scientists reported they had started a trial to genetically modify T-cells from 10 adult patients with lung cancer and reinject the modified T-cells back into their bodies to attack the cancer cells. The T-cells had the PD-1 protein (which stops or slows the immune response) removed using CRISPR-Cas9.[136][137]

A 2016 Cochrane systematic review looking at data from four trials on topical cystic fibrosis transmembrane conductance regulator (CFTR) gene therapy does not support its clinical use as a mist inhaled into the lungs to treat cystic fibrosis patients with lung infections. One of the four trials did find weak evidence that liposome-based CFTR gene transfer therapy may lead to a small respiratory improvement for people with CF. This weak evidence is not enough to make a clinical recommendation for routine CFTR gene therapy.[138]

In February Kite Pharma announced results from a clinical trial of CAR-T cells in around a hundred people with advanced Non-Hodgkin lymphoma.[139]

In March, French scientists reported on clinical research of gene therapy to treat sickle-cell disease.[140]

In August, the FDA approved tisagenlecleucel for acute lymphoblastic leukemia.[141] Tisagenlecleucel is an adoptive cell transfer therapy for B-cell acute lymphoblastic leukemia; T cells from a person with cancer are removed, genetically engineered to make a specific T-cell receptor (a chimeric T cell receptor, or “CAR-T”) that reacts to the cancer, and are administered back to the person. The T cells are engineered to target a protein called CD19 that is common on B cells. This is the first form of gene therapy to be approved in the United States. In October, a similar therapy called axicabtagene ciloleucel was approved for non-Hodgkin lymphoma.[142]

In December the results of using an adeno-associated virus with blood clotting factor VIII to treat nine haemophilia A patients were published. Six of the seven patients on the high dose regime increased the level of the blood clotting VIII to normal levels. The low and medium dose regimes had no effect on the patient’s blood clotting levels.[143][144]

In December, the FDA approved Luxturna, the first in vivo gene therapy, for the treatment of blindness due to Leber’s congenital amaurosis.[145] The price of this treatment was 850,000 US dollars for both eyes.[146][147]

Speculated uses for gene therapy include:

Gene Therapy techniques have the potential to provide alternative treatments for those with infertility. Recently, successful experimentation on mice has proven that fertility can be restored by using the gene therapy method, CRISPR.[148] Spermatogenical stem cells from another organism were transplanted into the testes of an infertile male mouse. The stem cells re-established spermatogenesis and fertility.[149]

Athletes might adopt gene therapy technologies to improve their performance.[150] Gene doping is not known to occur, but multiple gene therapies may have such effects. Kayser et al. argue that gene doping could level the playing field if all athletes receive equal access. Critics claim that any therapeutic intervention for non-therapeutic/enhancement purposes compromises the ethical foundations of medicine and sports.[151]

Genetic engineering could be used to cure diseases, but also to change physical appearance, metabolism, and even improve physical capabilities and mental faculties such as memory and intelligence. Ethical claims about germline engineering include beliefs that every fetus has a right to remain genetically unmodified, that parents hold the right to genetically modify their offspring, and that every child has the right to be born free of preventable diseases.[152][153][154] For parents, genetic engineering could be seen as another child enhancement technique to add to diet, exercise, education, training, cosmetics, and plastic surgery.[155][156] Another theorist claims that moral concerns limit but do not prohibit germline engineering.[157]

Possible regulatory schemes include a complete ban, provision to everyone, or professional self-regulation. The American Medical Associations Council on Ethical and Judicial Affairs stated that “genetic interventions to enhance traits should be considered permissible only in severely restricted situations: (1) clear and meaningful benefits to the fetus or child; (2) no trade-off with other characteristics or traits; and (3) equal access to the genetic technology, irrespective of income or other socioeconomic characteristics.”[158]

As early in the history of biotechnology as 1990, there have been scientists opposed to attempts to modify the human germline using these new tools,[159] and such concerns have continued as technology progressed.[160][161] With the advent of new techniques like CRISPR, in March 2015 a group of scientists urged a worldwide moratorium on clinical use of gene editing technologies to edit the human genome in a way that can be inherited.[124][125][126][127] In April 2015, researchers sparked controversy when they reported results of basic research to edit the DNA of non-viable human embryos using CRISPR.[148][162] A committee of the American National Academy of Sciences and National Academy of Medicine gave qualified support to human genome editing in 2017[163][164] once answers have been found to safety and efficiency problems “but only for serious conditions under stringent oversight.”[165]

Regulations covering genetic modification are part of general guidelines about human-involved biomedical research. There are no international treaties which are legally binding in this area, but there are recommendations for national laws from various bodies.

The Helsinki Declaration (Ethical Principles for Medical Research Involving Human Subjects) was amended by the World Medical Association’s General Assembly in 2008. This document provides principles physicians and researchers must consider when involving humans as research subjects. The Statement on Gene Therapy Research initiated by the Human Genome Organization (HUGO) in 2001 provides a legal baseline for all countries. HUGOs document emphasizes human freedom and adherence to human rights, and offers recommendations for somatic gene therapy, including the importance of recognizing public concerns about such research.[166]

No federal legislation lays out protocols or restrictions about human genetic engineering. This subject is governed by overlapping regulations from local and federal agencies, including the Department of Health and Human Services, the FDA and NIH’s Recombinant DNA Advisory Committee. Researchers seeking federal funds for an investigational new drug application, (commonly the case for somatic human genetic engineering,) must obey international and federal guidelines for the protection of human subjects.[167]

NIH serves as the main gene therapy regulator for federally funded research. Privately funded research is advised to follow these regulations. NIH provides funding for research that develops or enhances genetic engineering techniques and to evaluate the ethics and quality in current research. The NIH maintains a mandatory registry of human genetic engineering research protocols that includes all federally funded projects.

An NIH advisory committee published a set of guidelines on gene manipulation.[168] The guidelines discuss lab safety as well as human test subjects and various experimental types that involve genetic changes. Several sections specifically pertain to human genetic engineering, including Section III-C-1. This section describes required review processes and other aspects when seeking approval to begin clinical research involving genetic transfer into a human patient.[169] The protocol for a gene therapy clinical trial must be approved by the NIH’s Recombinant DNA Advisory Committee prior to any clinical trial beginning; this is different from any other kind of clinical trial.[168]

As with other kinds of drugs, the FDA regulates the quality and safety of gene therapy products and supervises how these products are used clinically. Therapeutic alteration of the human genome falls under the same regulatory requirements as any other medical treatment. Research involving human subjects, such as clinical trials, must be reviewed and approved by the FDA and an Institutional Review Board.[170][171]

Gene therapy is the basis for the plotline of the film I Am Legend[172] and the TV show Will Gene Therapy Change the Human Race?.[173] In 1994, gene therapy was a plot element in The Erlenmeyer Flask, The X-Files’ first season finale. It is also used in Stargate as a means of allowing humans to use Ancient technology.[174]

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Gene therapy – Wikipedia

Human Genetic Engineering Effects

Some people can think of Human Genetic Engineering as a thing that makes them live a healthier life for a long time. People can think of it as a something straight from the heaven or a programmed human being. Genetic engineering is a concept that can be used for enhancing the life of human beings.

However, Human Genetic Engineering Effects are also there that can harm humans. A lot of doctors or scientists involved in gene engineering believe that if the research produces accurate and effective manipulation of DNA in the humans, then they can make medicines for diseases that have no cure. This will also enable the doctors to make changes in the genes of a child before the birth of that child, so there will be no defects on a child from birth.

This process can also be applied on curing hereditary disease. It will prevent the disease from carrying forward to other coming generations. This research primarily focused on being applied on families that have a history of suffering from diseases. It will fix the wrong positioning of the genes. TheHuman Genetic Engineering Effects are in its application towards animals and plants that have been modified genetically. When farmers make use of gene-engineering for breeding plants, then this will result in fast production of food items. Fast and increased production will also put down the prices of several food items. Human Genetic Engineering can also add taste and nutrition to different food items.

Human Genetic Engineering Effects can also help in fighting with severe uncured diseases. Those who suffer from life threatening diseases like cancer or AIDS can have a better idea about maintaining their lives according to the circumstances. This can only be done with the help of Human Genetic Engineering.

Hereditary diseases will not trouble any person, and nor there will be any fear of deadly virus taking place in people on all corners of the world. Human Genetic Engineering can achieve all these things in a theoretical way. Human Genetic Engineering Effects can also be seen in societies concerning health. It has tremendous benefits on health.

Human Genetic Engineering can help people in fighting with cystic fibrosis problems. It also helps to fight against diabetes, and many other specific diseases. Bubble boy is also a disease that can be treated successfully with the help Human Genetic Engineering. It is also termed as Severe Combined Immune efficiency.

Gene mutation is the only thing responsible for the characterization of this deadly disease. This mutation causes ADA deficiencies that later result in destroying the immune system cells. Human Genetic Engineering Effects include ecological problems that might be present in organisms developed or generated by Human Genetic Engineering. However, it can leave positive impacts on a lot of diseases.

One cannot predict the changes that can occur with the use of species that generates with the help of Human Genetic Engineering Effects. A newly generated species creates ecology imbalances due to Human Genetic Engineering Effects. This is a similar case with exotic or natural species.

Human Genetic Engineering Effects

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Human Genetic Engineering Effects

Human Genetic Engineering Pros And Cons

Many human genetic engineering pros and cons are there that have stayed the same since its introduction to humanity. When the humans started harnessing the atomic powers, then just few years later they also start recognizing the effects of human genetic engineering on mankind. Many scientists have a belief that gene therapy can be a mainstream for saving lives of many people. A lot of human genetic engineering pros and cons have been involved since the evolution of genetic engineering. Mentioned below are some important advantages or pros of genetic engineering:

Other human genetic engineering pros and cons include the desirable characteristics in different plants and animals at the same time convenient. One can also do the manipulation of genes in trees or big plants. This will enable the trees to absorb increased amount of carbon dioxide, and it will reduce the effects of global warming. However, there is a question from critics that whether man has the right to do such manipulations or alterations in the genes of natural things.

With human genetic engineering, there is always a chance for altering the wheat plants genetics, which will then enable it to grow insulin. Human genetic engineering pros and cons have been among the concern of a lot of people involved in genetic engineering. Likewise the pros, certain cons are there of using the genetic engineering. Mentioned below are the cons of human genetic engineering:

The evolution of genetic engineering gets the consideration of being the biggest breakthroughs in the history of mankind after the evolution of atomic energy, and few other scientific discoveries. However, human genetic engineering pros and cons together have contributed a lot in creating a controversial image of it among the people.

All these eventualities have forced the government of many countries to make strict legislation laws to put restrictions on different experiment being made on human genetic engineering. They have made this decision by considering different human genetic engineering pros and cons.

Human Genetic Engineering Pros And Cons

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Human Genetic Engineering Pros And Cons

Gene therapy – Wikipedia

In the medicine field, gene therapy (also called human gene transfer) is the therapeutic delivery of nucleic acid into a patient’s cells as a drug to treat disease.[1][2] The first attempt at modifying human DNA was performed in 1980 by Martin Cline, but the first successful nuclear gene transfer in humans, approved by the National Institutes of Health, was performed in May 1989.[3] The first therapeutic use of gene transfer as well as the first direct insertion of human DNA into the nuclear genome was performed by French Anderson in a trial starting in September 1990.

Between 1989 and February 2016, over 2,300 clinical trials had been conducted, more than half of them in phase I.[4]

Not all medical procedures that introduce alterations to a patient’s genetic makeup can be considered gene therapy. Bone marrow transplantation and organ transplants in general have been found to introduce foreign DNA into patients.[5] Gene therapy is defined by the precision of the procedure and the intention of direct therapeutic effects.

Gene therapy was conceptualized in 1972, by authors who urged caution before commencing human gene therapy studies.

The first attempt, an unsuccessful one, at gene therapy (as well as the first case of medical transfer of foreign genes into humans not counting organ transplantation) was performed by Martin Cline on 10 July 1980.[6][7] Cline claimed that one of the genes in his patients was active six months later, though he never published this data or had it verified[8] and even if he is correct, it’s unlikely it produced any significant beneficial effects treating beta-thalassemia.

After extensive research on animals throughout the 1980s and a 1989 bacterial gene tagging trial on humans, the first gene therapy widely accepted as a success was demonstrated in a trial that started on 14 September 1990, when Ashi DeSilva was treated for ADA-SCID.[9]

The first somatic treatment that produced a permanent genetic change was performed in 1993.[citation needed]

Gene therapy is a way to fix a genetic problem at its source. The polymers are either translated into proteins, interfere with target gene expression, or possibly correct genetic mutations.

The most common form uses DNA that encodes a functional, therapeutic gene to replace a mutated gene. The polymer molecule is packaged within a “vector”, which carries the molecule inside cells.

Early clinical failures led to dismissals of gene therapy. Clinical successes since 2006 regained researchers’ attention, although as of 2014, it was still largely an experimental technique.[10] These include treatment of retinal diseases Leber’s congenital amaurosis[11][12][13][14] and choroideremia,[15] X-linked SCID,[16] ADA-SCID,[17][18] adrenoleukodystrophy,[19] chronic lymphocytic leukemia (CLL),[20] acute lymphocytic leukemia (ALL),[21] multiple myeloma,[22] haemophilia,[18] and Parkinson’s disease.[23] Between 2013 and April 2014, US companies invested over $600 million in the field.[24]

The first commercial gene therapy, Gendicine, was approved in China in 2003 for the treatment of certain cancers.[25] In 2011 Neovasculgen was registered in Russia as the first-in-class gene-therapy drug for treatment of peripheral artery disease, including critical limb ischemia.[26] In 2012 Glybera, a treatment for a rare inherited disorder, became the first treatment to be approved for clinical use in either Europe or the United States after its endorsement by the European Commission.[10][27]

Following early advances in genetic engineering of bacteria, cells, and small animals, scientists started considering how to apply it to medicine. Two main approaches were considered replacing or disrupting defective genes.[28] Scientists focused on diseases caused by single-gene defects, such as cystic fibrosis, haemophilia, muscular dystrophy, thalassemia, and sickle cell anemia. Glybera treats one such disease, caused by a defect in lipoprotein lipase.[27]

DNA must be administered, reach the damaged cells, enter the cell and either express or disrupt a protein.[29] Multiple delivery techniques have been explored. The initial approach incorporated DNA into an engineered virus to deliver the DNA into a chromosome.[30][31] Naked DNA approaches have also been explored, especially in the context of vaccine development.[32]

Generally, efforts focused on administering a gene that causes a needed protein to be expressed. More recently, increased understanding of nuclease function has led to more direct DNA editing, using techniques such as zinc finger nucleases and CRISPR. The vector incorporates genes into chromosomes. The expressed nucleases then knock out and replace genes in the chromosome. As of 2014 these approaches involve removing cells from patients, editing a chromosome and returning the transformed cells to patients.[33]

Gene editing is a potential approach to alter the human genome to treat genetic diseases,[34] viral diseases,[35] and cancer.[36] As of 2016 these approaches were still years from being medicine.[37][38]

Gene therapy may be classified into two types:

In somatic cell gene therapy (SCGT), the therapeutic genes are transferred into any cell other than a gamete, germ cell, gametocyte, or undifferentiated stem cell. Any such modifications affect the individual patient only, and are not inherited by offspring. Somatic gene therapy represents mainstream basic and clinical research, in which therapeutic DNA (either integrated in the genome or as an external episome or plasmid) is used to treat disease.

Over 600 clinical trials utilizing SCGT are underway in the US. Most focus on severe genetic disorders, including immunodeficiencies, haemophilia, thalassaemia, and cystic fibrosis. Such single gene disorders are good candidates for somatic cell therapy. The complete correction of a genetic disorder or the replacement of multiple genes is not yet possible. Only a few of the trials are in the advanced stages.[39]

In germline gene therapy (GGT), germ cells (sperm or egg cells) are modified by the introduction of functional genes into their genomes. Modifying a germ cell causes all the organism’s cells to contain the modified gene. The change is therefore heritable and passed on to later generations. Australia, Canada, Germany, Israel, Switzerland, and the Netherlands[40] prohibit GGT for application in human beings, for technical and ethical reasons, including insufficient knowledge about possible risks to future generations[40] and higher risks versus SCGT.[41] The US has no federal controls specifically addressing human genetic modification (beyond FDA regulations for therapies in general).[40][42][43][44]

The delivery of DNA into cells can be accomplished by multiple methods. The two major classes are recombinant viruses (sometimes called biological nanoparticles or viral vectors) and naked DNA or DNA complexes (non-viral methods).

In order to replicate, viruses introduce their genetic material into the host cell, tricking the host’s cellular machinery into using it as blueprints for viral proteins. Retroviruses go a stage further by having their genetic material copied into the genome of the host cell. Scientists exploit this by substituting a virus’s genetic material with therapeutic DNA. (The term ‘DNA’ may be an oversimplification, as some viruses contain RNA, and gene therapy could take this form as well.) A number of viruses have been used for human gene therapy, including retroviruses, adenoviruses, herpes simplex, vaccinia, and adeno-associated virus.[4] Like the genetic material (DNA or RNA) in viruses, therapeutic DNA can be designed to simply serve as a temporary blueprint that is degraded naturally or (at least theoretically) to enter the host’s genome, becoming a permanent part of the host’s DNA in infected cells.

Non-viral methods present certain advantages over viral methods, such as large scale production and low host immunogenicity. However, non-viral methods initially produced lower levels of transfection and gene expression, and thus lower therapeutic efficacy. Later technology remedied this deficiency.[citation needed]

Methods for non-viral gene therapy include the injection of naked DNA, electroporation, the gene gun, sonoporation, magnetofection, the use of oligonucleotides, lipoplexes, dendrimers, and inorganic nanoparticles.

Some of the unsolved problems include:

Three patients’ deaths have been reported in gene therapy trials, putting the field under close scrutiny. The first was that of Jesse Gelsinger in 1999. Jesse Gelsinger died because of immune rejection response.[51] One X-SCID patient died of leukemia in 2003.[9] In 2007, a rheumatoid arthritis patient died from an infection; the subsequent investigation concluded that the death was not related to gene therapy.[52]

In 1972 Friedmann and Roblin authored a paper in Science titled “Gene therapy for human genetic disease?”[53] Rogers (1970) was cited for proposing that exogenous good DNA be used to replace the defective DNA in those who suffer from genetic defects.[54]

In 1984 a retrovirus vector system was designed that could efficiently insert foreign genes into mammalian chromosomes.[55]

The first approved gene therapy clinical research in the US took place on 14 September 1990, at the National Institutes of Health (NIH), under the direction of William French Anderson.[56] Four-year-old Ashanti DeSilva received treatment for a genetic defect that left her with ADA-SCID, a severe immune system deficiency. The defective gene of the patient’s blood cells was replaced by the functional variant. Ashantis immune system was partially restored by the therapy. Production of the missing enzyme was temporarily stimulated, but the new cells with functional genes were not generated. She led a normal life only with the regular injections performed every two months. The effects were successful, but temporary.[57]

Cancer gene therapy was introduced in 1992/93 (Trojan et al. 1993).[58] The treatment of glioblastoma multiforme, the malignant brain tumor whose outcome is always fatal, was done using a vector expressing antisense IGF-I RNA (clinical trial approved by NIH protocolno.1602 November 24, 1993,[59] and by the FDA in 1994). This therapy also represents the beginning of cancer immunogene therapy, a treatment which proves to be effective due to the anti-tumor mechanism of IGF-I antisense, which is related to strong immune and apoptotic phenomena.

In 1992 Claudio Bordignon, working at the Vita-Salute San Raffaele University, performed the first gene therapy procedure using hematopoietic stem cells as vectors to deliver genes intended to correct hereditary diseases.[60] In 2002 this work led to the publication of the first successful gene therapy treatment for adenosine deaminase deficiency (ADA-SCID). The success of a multi-center trial for treating children with SCID (severe combined immune deficiency or “bubble boy” disease) from 2000 and 2002, was questioned when two of the ten children treated at the trial’s Paris center developed a leukemia-like condition. Clinical trials were halted temporarily in 2002, but resumed after regulatory review of the protocol in the US, the United Kingdom, France, Italy, and Germany.[61]

In 1993 Andrew Gobea was born with SCID following prenatal genetic screening. Blood was removed from his mother’s placenta and umbilical cord immediately after birth, to acquire stem cells. The allele that codes for adenosine deaminase (ADA) was obtained and inserted into a retrovirus. Retroviruses and stem cells were mixed, after which the viruses inserted the gene into the stem cell chromosomes. Stem cells containing the working ADA gene were injected into Andrew’s blood. Injections of the ADA enzyme were also given weekly. For four years T cells (white blood cells), produced by stem cells, made ADA enzymes using the ADA gene. After four years more treatment was needed.[62]

Jesse Gelsinger’s death in 1999 impeded gene therapy research in the US.[63][64] As a result, the FDA suspended several clinical trials pending the reevaluation of ethical and procedural practices.[65]

The modified cancer gene therapy strategy of antisense IGF-I RNA (NIH n 1602)[59] using antisense / triple helix anti-IGF-I approach was registered in 2002 by Wiley gene therapy clinical trial – n 635 and 636. The approach has shown promising results in the treatment of six different malignant tumors: glioblastoma, cancers of liver, colon, prostate, uterus, and ovary (Collaborative NATO Science Programme on Gene Therapy USA, France, Poland n LST 980517 conducted by J. Trojan) (Trojan et al., 2012). This anti-gene antisense/triple helix therapy has proven to be efficient, due to the mechanism stopping simultaneously IGF-I expression on translation and transcription levels, strengthening anti-tumor immune and apoptotic phenomena.

Sickle-cell disease can be treated in mice.[66] The mice which have essentially the same defect that causes human cases used a viral vector to induce production of fetal hemoglobin (HbF), which normally ceases to be produced shortly after birth. In humans, the use of hydroxyurea to stimulate the production of HbF temporarily alleviates sickle cell symptoms. The researchers demonstrated this treatment to be a more permanent means to increase therapeutic HbF production.[67]

A new gene therapy approach repaired errors in messenger RNA derived from defective genes. This technique has the potential to treat thalassaemia, cystic fibrosis and some cancers.[68]

Researchers created liposomes 25 nanometers across that can carry therapeutic DNA through pores in the nuclear membrane.[69]

In 2003 a research team inserted genes into the brain for the first time. They used liposomes coated in a polymer called polyethylene glycol, which unlike viral vectors, are small enough to cross the bloodbrain barrier.[70]

Short pieces of double-stranded RNA (short, interfering RNAs or siRNAs) are used by cells to degrade RNA of a particular sequence. If a siRNA is designed to match the RNA copied from a faulty gene, then the abnormal protein product of that gene will not be produced.[71]

Gendicine is a cancer gene therapy that delivers the tumor suppressor gene p53 using an engineered adenovirus. In 2003, it was approved in China for the treatment of head and neck squamous cell carcinoma.[25]

In March researchers announced the successful use of gene therapy to treat two adult patients for X-linked chronic granulomatous disease, a disease which affects myeloid cells and damages the immune system. The study is the first to show that gene therapy can treat the myeloid system.[72]

In May a team reported a way to prevent the immune system from rejecting a newly delivered gene.[73] Similar to organ transplantation, gene therapy has been plagued by this problem. The immune system normally recognizes the new gene as foreign and rejects the cells carrying it. The research utilized a newly uncovered network of genes regulated by molecules known as microRNAs. This natural function selectively obscured their therapeutic gene in immune system cells and protected it from discovery. Mice infected with the gene containing an immune-cell microRNA target sequence did not reject the gene.

In August scientists successfully treated metastatic melanoma in two patients using killer T cells genetically retargeted to attack the cancer cells.[74]

In November researchers reported on the use of VRX496, a gene-based immunotherapy for the treatment of HIV that uses a lentiviral vector to deliver an antisense gene against the HIV envelope. In a phase I clinical trial, five subjects with chronic HIV infection who had failed to respond to at least two antiretroviral regimens were treated. A single intravenous infusion of autologous CD4 T cells genetically modified with VRX496 was well tolerated. All patients had stable or decreased viral load; four of the five patients had stable or increased CD4 T cell counts. All five patients had stable or increased immune response to HIV antigens and other pathogens. This was the first evaluation of a lentiviral vector administered in a US human clinical trial.[75][76]

In May researchers announced the first gene therapy trial for inherited retinal disease. The first operation was carried out on a 23-year-old British male, Robert Johnson, in early 2007.[77]

Leber’s congenital amaurosis is an inherited blinding disease caused by mutations in the RPE65 gene. The results of a small clinical trial in children were published in April.[11] Delivery of recombinant adeno-associated virus (AAV) carrying RPE65 yielded positive results. In May two more groups reported positive results in independent clinical trials using gene therapy to treat the condition. In all three clinical trials, patients recovered functional vision without apparent side-effects.[11][12][13][14]

In September researchers were able to give trichromatic vision to squirrel monkeys.[78] In November 2009, researchers halted a fatal genetic disorder called adrenoleukodystrophy in two children using a lentivirus vector to deliver a functioning version of ABCD1, the gene that is mutated in the disorder.[79]

An April paper reported that gene therapy addressed achromatopsia (color blindness) in dogs by targeting cone photoreceptors. Cone function and day vision were restored for at least 33 months in two young specimens. The therapy was less efficient for older dogs.[80]

In September it was announced that an 18-year-old male patient in France with beta-thalassemia major had been successfully treated.[81] Beta-thalassemia major is an inherited blood disease in which beta haemoglobin is missing and patients are dependent on regular lifelong blood transfusions.[82] The technique used a lentiviral vector to transduce the human -globin gene into purified blood and marrow cells obtained from the patient in June 2007.[83] The patient’s haemoglobin levels were stable at 9 to 10 g/dL. About a third of the hemoglobin contained the form introduced by the viral vector and blood transfusions were not needed.[83][84] Further clinical trials were planned.[85] Bone marrow transplants are the only cure for thalassemia, but 75% of patients do not find a matching donor.[84]

Cancer immunogene therapy using modified antigene, antisense/triple helix approach was introduced in South America in 2010/11 in La Sabana University, Bogota (Ethical Committee 14 December 2010, no P-004-10). Considering the ethical aspect of gene diagnostic and gene therapy targeting IGF-I, the IGF-I expressing tumors i.e. lung and epidermis cancers were treated (Trojan et al. 2016).[86][87]

In 2007 and 2008, a man (Timothy Ray Brown) was cured of HIV by repeated hematopoietic stem cell transplantation (see also allogeneic stem cell transplantation, allogeneic bone marrow transplantation, allotransplantation) with double-delta-32 mutation which disables the CCR5 receptor. This cure was accepted by the medical community in 2011.[88] It required complete ablation of existing bone marrow, which is very debilitating.

In August two of three subjects of a pilot study were confirmed to have been cured from chronic lymphocytic leukemia (CLL). The therapy used genetically modified T cells to attack cells that expressed the CD19 protein to fight the disease.[20] In 2013, the researchers announced that 26 of 59 patients had achieved complete remission and the original patient had remained tumor-free.[89]

Human HGF plasmid DNA therapy of cardiomyocytes is being examined as a potential treatment for coronary artery disease as well as treatment for the damage that occurs to the heart after myocardial infarction.[90][91]

In 2011 Neovasculgen was registered in Russia as the first-in-class gene-therapy drug for treatment of peripheral artery disease, including critical limb ischemia; it delivers the gene encoding for VEGF.[92][26] Neovasculogen is a plasmid encoding the CMV promoter and the 165 amino acid form of VEGF.[93][94]

The FDA approved Phase 1 clinical trials on thalassemia major patients in the US for 10 participants in July.[95] The study was expected to continue until 2015.[85]

In July 2012, the European Medicines Agency recommended approval of a gene therapy treatment for the first time in either Europe or the United States. The treatment used Alipogene tiparvovec (Glybera) to compensate for lipoprotein lipase deficiency, which can cause severe pancreatitis.[96] The recommendation was endorsed by the European Commission in November 2012[10][27][97][98] and commercial rollout began in late 2014.[99] Alipogene tiparvovec was expected to cost around $1.6 million per treatment in 2012,[100] revised to $1 million in 2015,[101] making it the most expensive medicine in the world at the time.[102] As of 2016, only one person had been treated with drug.[103]

In December 2012, it was reported that 10 of 13 patients with multiple myeloma were in remission “or very close to it” three months after being injected with a treatment involving genetically engineered T cells to target proteins NY-ESO-1 and LAGE-1, which exist only on cancerous myeloma cells.[22]

In March researchers reported that three of five adult subjects who had acute lymphocytic leukemia (ALL) had been in remission for five months to two years after being treated with genetically modified T cells which attacked cells with CD19 genes on their surface, i.e. all B-cells, cancerous or not. The researchers believed that the patients’ immune systems would make normal T-cells and B-cells after a couple of months. They were also given bone marrow. One patient relapsed and died and one died of a blood clot unrelated to the disease.[21]

Following encouraging Phase 1 trials, in April, researchers announced they were starting Phase 2 clinical trials (called CUPID2 and SERCA-LVAD) on 250 patients[104] at several hospitals to combat heart disease. The therapy was designed to increase the levels of SERCA2, a protein in heart muscles, improving muscle function.[105] The FDA granted this a Breakthrough Therapy Designation to accelerate the trial and approval process.[106] In 2016 it was reported that no improvement was found from the CUPID 2 trial.[107]

In July researchers reported promising results for six children with two severe hereditary diseases had been treated with a partially deactivated lentivirus to replace a faulty gene and after 732 months. Three of the children had metachromatic leukodystrophy, which causes children to lose cognitive and motor skills.[108] The other children had Wiskott-Aldrich syndrome, which leaves them to open to infection, autoimmune diseases, and cancer.[109] Follow up trials with gene therapy on another six children with Wiskott-Aldrich syndrome were also reported as promising.[110][111]

In October researchers reported that two children born with adenosine deaminase severe combined immunodeficiency disease (ADA-SCID) had been treated with genetically engineered stem cells 18 months previously and that their immune systems were showing signs of full recovery. Another three children were making progress.[18] In 2014 a further 18 children with ADA-SCID were cured by gene therapy.[112] ADA-SCID children have no functioning immune system and are sometimes known as “bubble children.”[18]

Also in October researchers reported that they had treated six hemophilia sufferers in early 2011 using an adeno-associated virus. Over two years later all six were producing clotting factor.[18][113]

In January researchers reported that six choroideremia patients had been treated with adeno-associated virus with a copy of REP1. Over a six-month to two-year period all had improved their sight.[114][115] By 2016, 32 patients had been treated with positive results and researchers were hopeful the treatment would be long-lasting.[15] Choroideremia is an inherited genetic eye disease with no approved treatment, leading to loss of sight.

In March researchers reported that 12 HIV patients had been treated since 2009 in a trial with a genetically engineered virus with a rare mutation (CCR5 deficiency) known to protect against HIV with promising results.[116][117]

Clinical trials of gene therapy for sickle cell disease were started in 2014.[118][119] There is a need for high quality randomised controlled trials assessing the risks and benefits involved with gene therapy for people with sickle cell disease.[120]

In February LentiGlobin BB305, a gene therapy treatment undergoing clinical trials for treatment of beta thalassemia gained FDA “breakthrough” status after several patients were able to forgo the frequent blood transfusions usually required to treat the disease.[121]

In March researchers delivered a recombinant gene encoding a broadly neutralizing antibody into monkeys infected with simian HIV; the monkeys’ cells produced the antibody, which cleared them of HIV. The technique is named immunoprophylaxis by gene transfer (IGT). Animal tests for antibodies to ebola, malaria, influenza, and hepatitis were underway.[122][123]

In March, scientists, including an inventor of CRISPR, Jennifer Doudna, urged a worldwide moratorium on germline gene therapy, writing “scientists should avoid even attempting, in lax jurisdictions, germline genome modification for clinical application in humans” until the full implications “are discussed among scientific and governmental organizations”.[124][125][126][127]

In October, researchers announced that they had treated a baby girl, Layla Richards, with an experimental treatment using donor T-cells genetically engineered using TALEN to attack cancer cells. One year after the treatment she was still free of her cancer (a highly aggressive form of acute lymphoblastic leukaemia [ALL]).[128] Children with highly aggressive ALL normally have a very poor prognosis and Layla’s disease had been regarded as terminal before the treatment.[129]

In December, scientists of major world academies called for a moratorium on inheritable human genome edits, including those related to CRISPR-Cas9 technologies[130] but that basic research including embryo gene editing should continue.[131]

In April the Committee for Medicinal Products for Human Use of the European Medicines Agency endorsed a gene therapy treatment called Strimvelis[132][133] and the European Commission approved it in June.[134] This treats children born with adenosine deaminase deficiency and who have no functioning immune system. This was the second gene therapy treatment to be approved in Europe.[135]

In October, Chinese scientists reported they had started a trial to genetically modify T-cells from 10 adult patients with lung cancer and reinject the modified T-cells back into their bodies to attack the cancer cells. The T-cells had the PD-1 protein (which stops or slows the immune response) removed using CRISPR-Cas9.[136][137]

A 2016 Cochrane systematic review looking at data from four trials on topical cystic fibrosis transmembrane conductance regulator (CFTR) gene therapy does not support its clinical use as a mist inhaled into the lungs to treat cystic fibrosis patients with lung infections. One of the four trials did find weak evidence that liposome-based CFTR gene transfer therapy may lead to a small respiratory improvement for people with CF. This weak evidence is not enough to make a clinical recommendation for routine CFTR gene therapy.[138]

In February Kite Pharma announced results from a clinical trial of CAR-T cells in around a hundred people with advanced Non-Hodgkin lymphoma.[139]

In March, French scientists reported on clinical research of gene therapy to treat sickle-cell disease.[140]

In August, the FDA approved tisagenlecleucel for acute lymphoblastic leukemia.[141] Tisagenlecleucel is an adoptive cell transfer therapy for B-cell acute lymphoblastic leukemia; T cells from a person with cancer are removed, genetically engineered to make a specific T-cell receptor (a chimeric T cell receptor, or “CAR-T”) that reacts to the cancer, and are administered back to the person. The T cells are engineered to target a protein called CD19 that is common on B cells. This is the first form of gene therapy to be approved in the United States. In October, a similar therapy called axicabtagene ciloleucel was approved for non-Hodgkin lymphoma.[142]

In December the results of using an adeno-associated virus with blood clotting factor VIII to treat nine haemophilia A patients were published. Six of the seven patients on the high dose regime increased the level of the blood clotting VIII to normal levels. The low and medium dose regimes had no effect on the patient’s blood clotting levels.[143][144]

In December, the FDA approved Luxturna, the first in vivo gene therapy, for the treatment of blindness due to Leber’s congenital amaurosis.[145] The price of this treatment was 850,000 US dollars for both eyes.[146][147] CRISPR gene editing technology has also been used on mice to treat deafness due to the DFNA36 mutation, which also affects humans.[148]

Speculated uses for gene therapy include:

Gene Therapy techniques have the potential to provide alternative treatments for those with infertility. Recently, successful experimentation on mice has proven that fertility can be restored by using the gene therapy method, CRISPR.[149] Spermatogenical stem cells from another organism were transplanted into the testes of an infertile male mouse. The stem cells re-established spermatogenesis and fertility.[150]

Athletes might adopt gene therapy technologies to improve their performance.[151] Gene doping is not known to occur, but multiple gene therapies may have such effects. Kayser et al. argue that gene doping could level the playing field if all athletes receive equal access. Critics claim that any therapeutic intervention for non-therapeutic/enhancement purposes compromises the ethical foundations of medicine and sports.[152]

Genetic engineering could be used to cure diseases, but also to change physical appearance, metabolism, and even improve physical capabilities and mental faculties such as memory and intelligence. Ethical claims about germline engineering include beliefs that every fetus has a right to remain genetically unmodified, that parents hold the right to genetically modify their offspring, and that every child has the right to be born free of preventable diseases.[153][154][155] For parents, genetic engineering could be seen as another child enhancement technique to add to diet, exercise, education, training, cosmetics, and plastic surgery.[156][157] Another theorist claims that moral concerns limit but do not prohibit germline engineering.[158]

Possible regulatory schemes include a complete ban, provision to everyone, or professional self-regulation. The American Medical Associations Council on Ethical and Judicial Affairs stated that “genetic interventions to enhance traits should be considered permissible only in severely restricted situations: (1) clear and meaningful benefits to the fetus or child; (2) no trade-off with other characteristics or traits; and (3) equal access to the genetic technology, irrespective of income or other socioeconomic characteristics.”[159]

As early in the history of biotechnology as 1990, there have been scientists opposed to attempts to modify the human germline using these new tools,[160] and such concerns have continued as technology progressed.[161][162] With the advent of new techniques like CRISPR, in March 2015 a group of scientists urged a worldwide moratorium on clinical use of gene editing technologies to edit the human genome in a way that can be inherited.[124][125][126][127] In April 2015, researchers sparked controversy when they reported results of basic research to edit the DNA of non-viable human embryos using CRISPR.[149][163] A committee of the American National Academy of Sciences and National Academy of Medicine gave qualified support to human genome editing in 2017[164][165] once answers have been found to safety and efficiency problems “but only for serious conditions under stringent oversight.”[166]

Regulations covering genetic modification are part of general guidelines about human-involved biomedical research. There are no international treaties which are legally binding in this area, but there are recommendations for national laws from various bodies.

The Helsinki Declaration (Ethical Principles for Medical Research Involving Human Subjects) was amended by the World Medical Association’s General Assembly in 2008. This document provides principles physicians and researchers must consider when involving humans as research subjects. The Statement on Gene Therapy Research initiated by the Human Genome Organization (HUGO) in 2001 provides a legal baseline for all countries. HUGOs document emphasizes human freedom and adherence to human rights, and offers recommendations for somatic gene therapy, including the importance of recognizing public concerns about such research.[167]

No federal legislation lays out protocols or restrictions about human genetic engineering. This subject is governed by overlapping regulations from local and federal agencies, including the Department of Health and Human Services, the FDA and NIH’s Recombinant DNA Advisory Committee. Researchers seeking federal funds for an investigational new drug application, (commonly the case for somatic human genetic engineering,) must obey international and federal guidelines for the protection of human subjects.[168]

NIH serves as the main gene therapy regulator for federally funded research. Privately funded research is advised to follow these regulations. NIH provides funding for research that develops or enhances genetic engineering techniques and to evaluate the ethics and quality in current research. The NIH maintains a mandatory registry of human genetic engineering research protocols that includes all federally funded projects.

An NIH advisory committee published a set of guidelines on gene manipulation.[169] The guidelines discuss lab safety as well as human test subjects and various experimental types that involve genetic changes. Several sections specifically pertain to human genetic engineering, including Section III-C-1. This section describes required review processes and other aspects when seeking approval to begin clinical research involving genetic transfer into a human patient.[170] The protocol for a gene therapy clinical trial must be approved by the NIH’s Recombinant DNA Advisory Committee prior to any clinical trial beginning; this is different from any other kind of clinical trial.[169]

As with other kinds of drugs, the FDA regulates the quality and safety of gene therapy products and supervises how these products are used clinically. Therapeutic alteration of the human genome falls under the same regulatory requirements as any other medical treatment. Research involving human subjects, such as clinical trials, must be reviewed and approved by the FDA and an Institutional Review Board.[171][172]

Gene therapy is the basis for the plotline of the film I Am Legend[173] and the TV show Will Gene Therapy Change the Human Race?.[174] In 1994, gene therapy was a plot element in The Erlenmeyer Flask, The X-Files’ first season finale. It is also used in Stargate as a means of allowing humans to use Ancient technology.[175]

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Gene therapy – Wikipedia

Human Genetic Engineering Effects

Some people can think of Human Genetic Engineering as a thing that makes them live a healthier life for a long time. People can think of it as a something straight from the heaven or a programmed human being. Genetic engineering is a concept that can be used for enhancing the life of human beings.

However, Human Genetic Engineering Effects are also there that can harm humans. A lot of doctors or scientists involved in gene engineering believe that if the research produces accurate and effective manipulation of DNA in the humans, then they can make medicines for diseases that have no cure. This will also enable the doctors to make changes in the genes of a child before the birth of that child, so there will be no defects on a child from birth.

This process can also be applied on curing hereditary disease. It will prevent the disease from carrying forward to other coming generations. This research primarily focused on being applied on families that have a history of suffering from diseases. It will fix the wrong positioning of the genes. TheHuman Genetic Engineering Effects are in its application towards animals and plants that have been modified genetically. When farmers make use of gene-engineering for breeding plants, then this will result in fast production of food items. Fast and increased production will also put down the prices of several food items. Human Genetic Engineering can also add taste and nutrition to different food items.

Human Genetic Engineering Effects can also help in fighting with severe uncured diseases. Those who suffer from life threatening diseases like cancer or AIDS can have a better idea about maintaining their lives according to the circumstances. This can only be done with the help of Human Genetic Engineering.

Hereditary diseases will not trouble any person, and nor there will be any fear of deadly virus taking place in people on all corners of the world. Human Genetic Engineering can achieve all these things in a theoretical way. Human Genetic Engineering Effects can also be seen in societies concerning health. It has tremendous benefits on health.

Human Genetic Engineering can help people in fighting with cystic fibrosis problems. It also helps to fight against diabetes, and many other specific diseases. Bubble boy is also a disease that can be treated successfully with the help Human Genetic Engineering. It is also termed as Severe Combined Immune efficiency.

Gene mutation is the only thing responsible for the characterization of this deadly disease. This mutation causes ADA deficiencies that later result in destroying the immune system cells. Human Genetic Engineering Effects include ecological problems that might be present in organisms developed or generated by Human Genetic Engineering. However, it can leave positive impacts on a lot of diseases.

One cannot predict the changes that can occur with the use of species that generates with the help of Human Genetic Engineering Effects. A newly generated species creates ecology imbalances due to Human Genetic Engineering Effects. This is a similar case with exotic or natural species.

Human Genetic Engineering Effects

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Human Genetic Engineering Effects

Human Genetic Engineering Pros And Cons

Many human genetic engineering pros and cons are there that have stayed the same since its introduction to humanity. When the humans started harnessing the atomic powers, then just few years later they also start recognizing the effects of human genetic engineering on mankind. Many scientists have a belief that gene therapy can be a mainstream for saving lives of many people. A lot of human genetic engineering pros and cons have been involved since the evolution of genetic engineering. Mentioned below are some important advantages or pros of genetic engineering:

Other human genetic engineering pros and cons include the desirable characteristics in different plants and animals at the same time convenient. One can also do the manipulation of genes in trees or big plants. This will enable the trees to absorb increased amount of carbon dioxide, and it will reduce the effects of global warming. However, there is a question from critics that whether man has the right to do such manipulations or alterations in the genes of natural things.

With human genetic engineering, there is always a chance for altering the wheat plants genetics, which will then enable it to grow insulin. Human genetic engineering pros and cons have been among the concern of a lot of people involved in genetic engineering. Likewise the pros, certain cons are there of using the genetic engineering. Mentioned below are the cons of human genetic engineering:

The evolution of genetic engineering gets the consideration of being the biggest breakthroughs in the history of mankind after the evolution of atomic energy, and few other scientific discoveries. However, human genetic engineering pros and cons together have contributed a lot in creating a controversial image of it among the people.

All these eventualities have forced the government of many countries to make strict legislation laws to put restrictions on different experiment being made on human genetic engineering. They have made this decision by considering different human genetic engineering pros and cons.

Human Genetic Engineering Pros And Cons

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Human Genetic Engineering Pros And Cons

Gene therapy – Wikipedia

In the medicine field, gene therapy (also called human gene transfer) is the therapeutic delivery of nucleic acid into a patient’s cells as a drug to treat disease.[1][2] The first attempt at modifying human DNA was performed in 1980 by Martin Cline, but the first successful nuclear gene transfer in humans, approved by the National Institutes of Health, was performed in May 1989.[3] The first therapeutic use of gene transfer as well as the first direct insertion of human DNA into the nuclear genome was performed by French Anderson in a trial starting in September 1990.

Between 1989 and February 2016, over 2,300 clinical trials had been conducted, more than half of them in phase I.[4]

Not all medical procedures that introduce alterations to a patient’s genetic makeup can be considered gene therapy. Bone marrow transplantation and organ transplants in general have been found to introduce foreign DNA into patients.[5] Gene therapy is defined by the precision of the procedure and the intention of direct therapeutic effects.

Gene therapy was conceptualized in 1972, by authors who urged caution before commencing human gene therapy studies.

The first attempt, an unsuccessful one, at gene therapy (as well as the first case of medical transfer of foreign genes into humans not counting organ transplantation) was performed by Martin Cline on 10 July 1980.[6][7] Cline claimed that one of the genes in his patients was active six months later, though he never published this data or had it verified[8] and even if he is correct, it’s unlikely it produced any significant beneficial effects treating beta-thalassemia.

After extensive research on animals throughout the 1980s and a 1989 bacterial gene tagging trial on humans, the first gene therapy widely accepted as a success was demonstrated in a trial that started on 14 September 1990, when Ashi DeSilva was treated for ADA-SCID.[9]

The first somatic treatment that produced a permanent genetic change was performed in 1993.[citation needed]

Gene therapy is a way to fix a genetic problem at its source. The polymers are either translated into proteins, interfere with target gene expression, or possibly correct genetic mutations.

The most common form uses DNA that encodes a functional, therapeutic gene to replace a mutated gene. The polymer molecule is packaged within a “vector”, which carries the molecule inside cells.

Early clinical failures led to dismissals of gene therapy. Clinical successes since 2006 regained researchers’ attention, although as of 2014, it was still largely an experimental technique.[10] These include treatment of retinal diseases Leber’s congenital amaurosis[11][12][13][14] and choroideremia,[15] X-linked SCID,[16] ADA-SCID,[17][18] adrenoleukodystrophy,[19] chronic lymphocytic leukemia (CLL),[20] acute lymphocytic leukemia (ALL),[21] multiple myeloma,[22] haemophilia,[18] and Parkinson’s disease.[23] Between 2013 and April 2014, US companies invested over $600 million in the field.[24]

The first commercial gene therapy, Gendicine, was approved in China in 2003 for the treatment of certain cancers.[25] In 2011 Neovasculgen was registered in Russia as the first-in-class gene-therapy drug for treatment of peripheral artery disease, including critical limb ischemia.[26] In 2012 Glybera, a treatment for a rare inherited disorder, became the first treatment to be approved for clinical use in either Europe or the United States after its endorsement by the European Commission.[10][27]

Following early advances in genetic engineering of bacteria, cells, and small animals, scientists started considering how to apply it to medicine. Two main approaches were considered replacing or disrupting defective genes.[28] Scientists focused on diseases caused by single-gene defects, such as cystic fibrosis, haemophilia, muscular dystrophy, thalassemia, and sickle cell anemia. Glybera treats one such disease, caused by a defect in lipoprotein lipase.[27]

DNA must be administered, reach the damaged cells, enter the cell and either express or disrupt a protein.[29] Multiple delivery techniques have been explored. The initial approach incorporated DNA into an engineered virus to deliver the DNA into a chromosome.[30][31] Naked DNA approaches have also been explored, especially in the context of vaccine development.[32]

Generally, efforts focused on administering a gene that causes a needed protein to be expressed. More recently, increased understanding of nuclease function has led to more direct DNA editing, using techniques such as zinc finger nucleases and CRISPR. The vector incorporates genes into chromosomes. The expressed nucleases then knock out and replace genes in the chromosome. As of 2014 these approaches involve removing cells from patients, editing a chromosome and returning the transformed cells to patients.[33]

Gene editing is a potential approach to alter the human genome to treat genetic diseases,[34] viral diseases,[35] and cancer.[36] As of 2016 these approaches were still years from being medicine.[37][38]

Gene therapy may be classified into two types:

In somatic cell gene therapy (SCGT), the therapeutic genes are transferred into any cell other than a gamete, germ cell, gametocyte, or undifferentiated stem cell. Any such modifications affect the individual patient only, and are not inherited by offspring. Somatic gene therapy represents mainstream basic and clinical research, in which therapeutic DNA (either integrated in the genome or as an external episome or plasmid) is used to treat disease.

Over 600 clinical trials utilizing SCGT are underway in the US. Most focus on severe genetic disorders, including immunodeficiencies, haemophilia, thalassaemia, and cystic fibrosis. Such single gene disorders are good candidates for somatic cell therapy. The complete correction of a genetic disorder or the replacement of multiple genes is not yet possible. Only a few of the trials are in the advanced stages.[39]

In germline gene therapy (GGT), germ cells (sperm or egg cells) are modified by the introduction of functional genes into their genomes. Modifying a germ cell causes all the organism’s cells to contain the modified gene. The change is therefore heritable and passed on to later generations. Australia, Canada, Germany, Israel, Switzerland, and the Netherlands[40] prohibit GGT for application in human beings, for technical and ethical reasons, including insufficient knowledge about possible risks to future generations[40] and higher risks versus SCGT.[41] The US has no federal controls specifically addressing human genetic modification (beyond FDA regulations for therapies in general).[40][42][43][44]

The delivery of DNA into cells can be accomplished by multiple methods. The two major classes are recombinant viruses (sometimes called biological nanoparticles or viral vectors) and naked DNA or DNA complexes (non-viral methods).

In order to replicate, viruses introduce their genetic material into the host cell, tricking the host’s cellular machinery into using it as blueprints for viral proteins. Retroviruses go a stage further by having their genetic material copied into the genome of the host cell. Scientists exploit this by substituting a virus’s genetic material with therapeutic DNA. (The term ‘DNA’ may be an oversimplification, as some viruses contain RNA, and gene therapy could take this form as well.) A number of viruses have been used for human gene therapy, including retroviruses, adenoviruses, herpes simplex, vaccinia, and adeno-associated virus.[4] Like the genetic material (DNA or RNA) in viruses, therapeutic DNA can be designed to simply serve as a temporary blueprint that is degraded naturally or (at least theoretically) to enter the host’s genome, becoming a permanent part of the host’s DNA in infected cells.

Non-viral methods present certain advantages over viral methods, such as large scale production and low host immunogenicity. However, non-viral methods initially produced lower levels of transfection and gene expression, and thus lower therapeutic efficacy. Later technology remedied this deficiency.[citation needed]

Methods for non-viral gene therapy include the injection of naked DNA, electroporation, the gene gun, sonoporation, magnetofection, the use of oligonucleotides, lipoplexes, dendrimers, and inorganic nanoparticles.

Some of the unsolved problems include:

Three patients’ deaths have been reported in gene therapy trials, putting the field under close scrutiny. The first was that of Jesse Gelsinger in 1999. Jesse Gelsinger died because of immune rejection response.[51] One X-SCID patient died of leukemia in 2003.[9] In 2007, a rheumatoid arthritis patient died from an infection; the subsequent investigation concluded that the death was not related to gene therapy.[52]

In 1972 Friedmann and Roblin authored a paper in Science titled “Gene therapy for human genetic disease?”[53] Rogers (1970) was cited for proposing that exogenous good DNA be used to replace the defective DNA in those who suffer from genetic defects.[54]

In 1984 a retrovirus vector system was designed that could efficiently insert foreign genes into mammalian chromosomes.[55]

The first approved gene therapy clinical research in the US took place on 14 September 1990, at the National Institutes of Health (NIH), under the direction of William French Anderson.[56] Four-year-old Ashanti DeSilva received treatment for a genetic defect that left her with ADA-SCID, a severe immune system deficiency. The defective gene of the patient’s blood cells was replaced by the functional variant. Ashantis immune system was partially restored by the therapy. Production of the missing enzyme was temporarily stimulated, but the new cells with functional genes were not generated. She led a normal life only with the regular injections performed every two months. The effects were successful, but temporary.[57]

Cancer gene therapy was introduced in 1992/93 (Trojan et al. 1993).[58] The treatment of glioblastoma multiforme, the malignant brain tumor whose outcome is always fatal, was done using a vector expressing antisense IGF-I RNA (clinical trial approved by NIH protocolno.1602 November 24, 1993,[59] and by the FDA in 1994). This therapy also represents the beginning of cancer immunogene therapy, a treatment which proves to be effective due to the anti-tumor mechanism of IGF-I antisense, which is related to strong immune and apoptotic phenomena.

In 1992 Claudio Bordignon, working at the Vita-Salute San Raffaele University, performed the first gene therapy procedure using hematopoietic stem cells as vectors to deliver genes intended to correct hereditary diseases.[60] In 2002 this work led to the publication of the first successful gene therapy treatment for adenosine deaminase deficiency (ADA-SCID). The success of a multi-center trial for treating children with SCID (severe combined immune deficiency or “bubble boy” disease) from 2000 and 2002, was questioned when two of the ten children treated at the trial’s Paris center developed a leukemia-like condition. Clinical trials were halted temporarily in 2002, but resumed after regulatory review of the protocol in the US, the United Kingdom, France, Italy, and Germany.[61]

In 1993 Andrew Gobea was born with SCID following prenatal genetic screening. Blood was removed from his mother’s placenta and umbilical cord immediately after birth, to acquire stem cells. The allele that codes for adenosine deaminase (ADA) was obtained and inserted into a retrovirus. Retroviruses and stem cells were mixed, after which the viruses inserted the gene into the stem cell chromosomes. Stem cells containing the working ADA gene were injected into Andrew’s blood. Injections of the ADA enzyme were also given weekly. For four years T cells (white blood cells), produced by stem cells, made ADA enzymes using the ADA gene. After four years more treatment was needed.[62]

Jesse Gelsinger’s death in 1999 impeded gene therapy research in the US.[63][64] As a result, the FDA suspended several clinical trials pending the reevaluation of ethical and procedural practices.[65]

The modified cancer gene therapy strategy of antisense IGF-I RNA (NIH n 1602)[59] using antisense / triple helix anti-IGF-I approach was registered in 2002 by Wiley gene therapy clinical trial – n 635 and 636. The approach has shown promising results in the treatment of six different malignant tumors: glioblastoma, cancers of liver, colon, prostate, uterus, and ovary (Collaborative NATO Science Programme on Gene Therapy USA, France, Poland n LST 980517 conducted by J. Trojan) (Trojan et al., 2012). This anti-gene antisense/triple helix therapy has proven to be efficient, due to the mechanism stopping simultaneously IGF-I expression on translation and transcription levels, strengthening anti-tumor immune and apoptotic phenomena.

Sickle-cell disease can be treated in mice.[66] The mice which have essentially the same defect that causes human cases used a viral vector to induce production of fetal hemoglobin (HbF), which normally ceases to be produced shortly after birth. In humans, the use of hydroxyurea to stimulate the production of HbF temporarily alleviates sickle cell symptoms. The researchers demonstrated this treatment to be a more permanent means to increase therapeutic HbF production.[67]

A new gene therapy approach repaired errors in messenger RNA derived from defective genes. This technique has the potential to treat thalassaemia, cystic fibrosis and some cancers.[68]

Researchers created liposomes 25 nanometers across that can carry therapeutic DNA through pores in the nuclear membrane.[69]

In 2003 a research team inserted genes into the brain for the first time. They used liposomes coated in a polymer called polyethylene glycol, which unlike viral vectors, are small enough to cross the bloodbrain barrier.[70]

Short pieces of double-stranded RNA (short, interfering RNAs or siRNAs) are used by cells to degrade RNA of a particular sequence. If a siRNA is designed to match the RNA copied from a faulty gene, then the abnormal protein product of that gene will not be produced.[71]

Gendicine is a cancer gene therapy that delivers the tumor suppressor gene p53 using an engineered adenovirus. In 2003, it was approved in China for the treatment of head and neck squamous cell carcinoma.[25]

In March researchers announced the successful use of gene therapy to treat two adult patients for X-linked chronic granulomatous disease, a disease which affects myeloid cells and damages the immune system. The study is the first to show that gene therapy can treat the myeloid system.[72]

In May a team reported a way to prevent the immune system from rejecting a newly delivered gene.[73] Similar to organ transplantation, gene therapy has been plagued by this problem. The immune system normally recognizes the new gene as foreign and rejects the cells carrying it. The research utilized a newly uncovered network of genes regulated by molecules known as microRNAs. This natural function selectively obscured their therapeutic gene in immune system cells and protected it from discovery. Mice infected with the gene containing an immune-cell microRNA target sequence did not reject the gene.

In August scientists successfully treated metastatic melanoma in two patients using killer T cells genetically retargeted to attack the cancer cells.[74]

In November researchers reported on the use of VRX496, a gene-based immunotherapy for the treatment of HIV that uses a lentiviral vector to deliver an antisense gene against the HIV envelope. In a phase I clinical trial, five subjects with chronic HIV infection who had failed to respond to at least two antiretroviral regimens were treated. A single intravenous infusion of autologous CD4 T cells genetically modified with VRX496 was well tolerated. All patients had stable or decreased viral load; four of the five patients had stable or increased CD4 T cell counts. All five patients had stable or increased immune response to HIV antigens and other pathogens. This was the first evaluation of a lentiviral vector administered in a US human clinical trial.[75][76]

In May researchers announced the first gene therapy trial for inherited retinal disease. The first operation was carried out on a 23-year-old British male, Robert Johnson, in early 2007.[77]

Leber’s congenital amaurosis is an inherited blinding disease caused by mutations in the RPE65 gene. The results of a small clinical trial in children were published in April.[11] Delivery of recombinant adeno-associated virus (AAV) carrying RPE65 yielded positive results. In May two more groups reported positive results in independent clinical trials using gene therapy to treat the condition. In all three clinical trials, patients recovered functional vision without apparent side-effects.[11][12][13][14]

In September researchers were able to give trichromatic vision to squirrel monkeys.[78] In November 2009, researchers halted a fatal genetic disorder called adrenoleukodystrophy in two children using a lentivirus vector to deliver a functioning version of ABCD1, the gene that is mutated in the disorder.[79]

An April paper reported that gene therapy addressed achromatopsia (color blindness) in dogs by targeting cone photoreceptors. Cone function and day vision were restored for at least 33 months in two young specimens. The therapy was less efficient for older dogs.[80]

In September it was announced that an 18-year-old male patient in France with beta-thalassemia major had been successfully treated.[81] Beta-thalassemia major is an inherited blood disease in which beta haemoglobin is missing and patients are dependent on regular lifelong blood transfusions.[82] The technique used a lentiviral vector to transduce the human -globin gene into purified blood and marrow cells obtained from the patient in June 2007.[83] The patient’s haemoglobin levels were stable at 9 to 10 g/dL. About a third of the hemoglobin contained the form introduced by the viral vector and blood transfusions were not needed.[83][84] Further clinical trials were planned.[85] Bone marrow transplants are the only cure for thalassemia, but 75% of patients do not find a matching donor.[84]

Cancer immunogene therapy using modified antigene, antisense/triple helix approach was introduced in South America in 2010/11 in La Sabana University, Bogota (Ethical Committee 14 December 2010, no P-004-10). Considering the ethical aspect of gene diagnostic and gene therapy targeting IGF-I, the IGF-I expressing tumors i.e. lung and epidermis cancers were treated (Trojan et al. 2016).[86][87]

In 2007 and 2008, a man (Timothy Ray Brown) was cured of HIV by repeated hematopoietic stem cell transplantation (see also allogeneic stem cell transplantation, allogeneic bone marrow transplantation, allotransplantation) with double-delta-32 mutation which disables the CCR5 receptor. This cure was accepted by the medical community in 2011.[88] It required complete ablation of existing bone marrow, which is very debilitating.

In August two of three subjects of a pilot study were confirmed to have been cured from chronic lymphocytic leukemia (CLL). The therapy used genetically modified T cells to attack cells that expressed the CD19 protein to fight the disease.[20] In 2013, the researchers announced that 26 of 59 patients had achieved complete remission and the original patient had remained tumor-free.[89]

Human HGF plasmid DNA therapy of cardiomyocytes is being examined as a potential treatment for coronary artery disease as well as treatment for the damage that occurs to the heart after myocardial infarction.[90][91]

In 2011 Neovasculgen was registered in Russia as the first-in-class gene-therapy drug for treatment of peripheral artery disease, including critical limb ischemia; it delivers the gene encoding for VEGF.[92][26] Neovasculogen is a plasmid encoding the CMV promoter and the 165 amino acid form of VEGF.[93][94]

The FDA approved Phase 1 clinical trials on thalassemia major patients in the US for 10 participants in July.[95] The study was expected to continue until 2015.[85]

In July 2012, the European Medicines Agency recommended approval of a gene therapy treatment for the first time in either Europe or the United States. The treatment used Alipogene tiparvovec (Glybera) to compensate for lipoprotein lipase deficiency, which can cause severe pancreatitis.[96] The recommendation was endorsed by the European Commission in November 2012[10][27][97][98] and commercial rollout began in late 2014.[99] Alipogene tiparvovec was expected to cost around $1.6 million per treatment in 2012,[100] revised to $1 million in 2015,[101] making it the most expensive medicine in the world at the time.[102] As of 2016, only one person had been treated with drug.[103]

In December 2012, it was reported that 10 of 13 patients with multiple myeloma were in remission “or very close to it” three months after being injected with a treatment involving genetically engineered T cells to target proteins NY-ESO-1 and LAGE-1, which exist only on cancerous myeloma cells.[22]

In March researchers reported that three of five adult subjects who had acute lymphocytic leukemia (ALL) had been in remission for five months to two years after being treated with genetically modified T cells which attacked cells with CD19 genes on their surface, i.e. all B-cells, cancerous or not. The researchers believed that the patients’ immune systems would make normal T-cells and B-cells after a couple of months. They were also given bone marrow. One patient relapsed and died and one died of a blood clot unrelated to the disease.[21]

Following encouraging Phase 1 trials, in April, researchers announced they were starting Phase 2 clinical trials (called CUPID2 and SERCA-LVAD) on 250 patients[104] at several hospitals to combat heart disease. The therapy was designed to increase the levels of SERCA2, a protein in heart muscles, improving muscle function.[105] The FDA granted this a Breakthrough Therapy Designation to accelerate the trial and approval process.[106] In 2016 it was reported that no improvement was found from the CUPID 2 trial.[107]

In July researchers reported promising results for six children with two severe hereditary diseases had been treated with a partially deactivated lentivirus to replace a faulty gene and after 732 months. Three of the children had metachromatic leukodystrophy, which causes children to lose cognitive and motor skills.[108] The other children had Wiskott-Aldrich syndrome, which leaves them to open to infection, autoimmune diseases, and cancer.[109] Follow up trials with gene therapy on another six children with Wiskott-Aldrich syndrome were also reported as promising.[110][111]

In October researchers reported that two children born with adenosine deaminase severe combined immunodeficiency disease (ADA-SCID) had been treated with genetically engineered stem cells 18 months previously and that their immune systems were showing signs of full recovery. Another three children were making progress.[18] In 2014 a further 18 children with ADA-SCID were cured by gene therapy.[112] ADA-SCID children have no functioning immune system and are sometimes known as “bubble children.”[18]

Also in October researchers reported that they had treated six hemophilia sufferers in early 2011 using an adeno-associated virus. Over two years later all six were producing clotting factor.[18][113]

In January researchers reported that six choroideremia patients had been treated with adeno-associated virus with a copy of REP1. Over a six-month to two-year period all had improved their sight.[114][115] By 2016, 32 patients had been treated with positive results and researchers were hopeful the treatment would be long-lasting.[15] Choroideremia is an inherited genetic eye disease with no approved treatment, leading to loss of sight.

In March researchers reported that 12 HIV patients had been treated since 2009 in a trial with a genetically engineered virus with a rare mutation (CCR5 deficiency) known to protect against HIV with promising results.[116][117]

Clinical trials of gene therapy for sickle cell disease were started in 2014.[118][119] There is a need for high quality randomised controlled trials assessing the risks and benefits involved with gene therapy for people with sickle cell disease.[120]

In February LentiGlobin BB305, a gene therapy treatment undergoing clinical trials for treatment of beta thalassemia gained FDA “breakthrough” status after several patients were able to forgo the frequent blood transfusions usually required to treat the disease.[121]

In March researchers delivered a recombinant gene encoding a broadly neutralizing antibody into monkeys infected with simian HIV; the monkeys’ cells produced the antibody, which cleared them of HIV. The technique is named immunoprophylaxis by gene transfer (IGT). Animal tests for antibodies to ebola, malaria, influenza, and hepatitis were underway.[122][123]

In March, scientists, including an inventor of CRISPR, Jennifer Doudna, urged a worldwide moratorium on germline gene therapy, writing “scientists should avoid even attempting, in lax jurisdictions, germline genome modification for clinical application in humans” until the full implications “are discussed among scientific and governmental organizations”.[124][125][126][127]

In October, researchers announced that they had treated a baby girl, Layla Richards, with an experimental treatment using donor T-cells genetically engineered using TALEN to attack cancer cells. One year after the treatment she was still free of her cancer (a highly aggressive form of acute lymphoblastic leukaemia [ALL]).[128] Children with highly aggressive ALL normally have a very poor prognosis and Layla’s disease had been regarded as terminal before the treatment.[129]

In December, scientists of major world academies called for a moratorium on inheritable human genome edits, including those related to CRISPR-Cas9 technologies[130] but that basic research including embryo gene editing should continue.[131]

In April the Committee for Medicinal Products for Human Use of the European Medicines Agency endorsed a gene therapy treatment called Strimvelis[132][133] and the European Commission approved it in June.[134] This treats children born with adenosine deaminase deficiency and who have no functioning immune system. This was the second gene therapy treatment to be approved in Europe.[135]

In October, Chinese scientists reported they had started a trial to genetically modify T-cells from 10 adult patients with lung cancer and reinject the modified T-cells back into their bodies to attack the cancer cells. The T-cells had the PD-1 protein (which stops or slows the immune response) removed using CRISPR-Cas9.[136][137]

A 2016 Cochrane systematic review looking at data from four trials on topical cystic fibrosis transmembrane conductance regulator (CFTR) gene therapy does not support its clinical use as a mist inhaled into the lungs to treat cystic fibrosis patients with lung infections. One of the four trials did find weak evidence that liposome-based CFTR gene transfer therapy may lead to a small respiratory improvement for people with CF. This weak evidence is not enough to make a clinical recommendation for routine CFTR gene therapy.[138]

In February Kite Pharma announced results from a clinical trial of CAR-T cells in around a hundred people with advanced Non-Hodgkin lymphoma.[139]

In March, French scientists reported on clinical research of gene therapy to treat sickle-cell disease.[140]

In August, the FDA approved tisagenlecleucel for acute lymphoblastic leukemia.[141] Tisagenlecleucel is an adoptive cell transfer therapy for B-cell acute lymphoblastic leukemia; T cells from a person with cancer are removed, genetically engineered to make a specific T-cell receptor (a chimeric T cell receptor, or “CAR-T”) that reacts to the cancer, and are administered back to the person. The T cells are engineered to target a protein called CD19 that is common on B cells. This is the first form of gene therapy to be approved in the United States. In October, a similar therapy called axicabtagene ciloleucel was approved for non-Hodgkin lymphoma.[142]

In December the results of using an adeno-associated virus with blood clotting factor VIII to treat nine haemophilia A patients were published. Six of the seven patients on the high dose regime increased the level of the blood clotting VIII to normal levels. The low and medium dose regimes had no effect on the patient’s blood clotting levels.[143][144]

In December, the FDA approved Luxturna, the first in vivo gene therapy, for the treatment of blindness due to Leber’s congenital amaurosis.[145] The price of this treatment was 850,000 US dollars for both eyes.[146][147] CRISPR gene editing technology has also been used on mice to treat deafness due to the DFNA36 mutation, which also affects humans.[148]

Speculated uses for gene therapy include:

Gene Therapy techniques have the potential to provide alternative treatments for those with infertility. Recently, successful experimentation on mice has proven that fertility can be restored by using the gene therapy method, CRISPR.[149] Spermatogenical stem cells from another organism were transplanted into the testes of an infertile male mouse. The stem cells re-established spermatogenesis and fertility.[150]

Athletes might adopt gene therapy technologies to improve their performance.[151] Gene doping is not known to occur, but multiple gene therapies may have such effects. Kayser et al. argue that gene doping could level the playing field if all athletes receive equal access. Critics claim that any therapeutic intervention for non-therapeutic/enhancement purposes compromises the ethical foundations of medicine and sports.[152]

Genetic engineering could be used to cure diseases, but also to change physical appearance, metabolism, and even improve physical capabilities and mental faculties such as memory and intelligence. Ethical claims about germline engineering include beliefs that every fetus has a right to remain genetically unmodified, that parents hold the right to genetically modify their offspring, and that every child has the right to be born free of preventable diseases.[153][154][155] For parents, genetic engineering could be seen as another child enhancement technique to add to diet, exercise, education, training, cosmetics, and plastic surgery.[156][157] Another theorist claims that moral concerns limit but do not prohibit germline engineering.[158]

Possible regulatory schemes include a complete ban, provision to everyone, or professional self-regulation. The American Medical Associations Council on Ethical and Judicial Affairs stated that “genetic interventions to enhance traits should be considered permissible only in severely restricted situations: (1) clear and meaningful benefits to the fetus or child; (2) no trade-off with other characteristics or traits; and (3) equal access to the genetic technology, irrespective of income or other socioeconomic characteristics.”[159]

As early in the history of biotechnology as 1990, there have been scientists opposed to attempts to modify the human germline using these new tools,[160] and such concerns have continued as technology progressed.[161][162] With the advent of new techniques like CRISPR, in March 2015 a group of scientists urged a worldwide moratorium on clinical use of gene editing technologies to edit the human genome in a way that can be inherited.[124][125][126][127] In April 2015, researchers sparked controversy when they reported results of basic research to edit the DNA of non-viable human embryos using CRISPR.[149][163] A committee of the American National Academy of Sciences and National Academy of Medicine gave qualified support to human genome editing in 2017[164][165] once answers have been found to safety and efficiency problems “but only for serious conditions under stringent oversight.”[166]

Regulations covering genetic modification are part of general guidelines about human-involved biomedical research. There are no international treaties which are legally binding in this area, but there are recommendations for national laws from various bodies.

The Helsinki Declaration (Ethical Principles for Medical Research Involving Human Subjects) was amended by the World Medical Association’s General Assembly in 2008. This document provides principles physicians and researchers must consider when involving humans as research subjects. The Statement on Gene Therapy Research initiated by the Human Genome Organization (HUGO) in 2001 provides a legal baseline for all countries. HUGOs document emphasizes human freedom and adherence to human rights, and offers recommendations for somatic gene therapy, including the importance of recognizing public concerns about such research.[167]

No federal legislation lays out protocols or restrictions about human genetic engineering. This subject is governed by overlapping regulations from local and federal agencies, including the Department of Health and Human Services, the FDA and NIH’s Recombinant DNA Advisory Committee. Researchers seeking federal funds for an investigational new drug application, (commonly the case for somatic human genetic engineering,) must obey international and federal guidelines for the protection of human subjects.[168]

NIH serves as the main gene therapy regulator for federally funded research. Privately funded research is advised to follow these regulations. NIH provides funding for research that develops or enhances genetic engineering techniques and to evaluate the ethics and quality in current research. The NIH maintains a mandatory registry of human genetic engineering research protocols that includes all federally funded projects.

An NIH advisory committee published a set of guidelines on gene manipulation.[169] The guidelines discuss lab safety as well as human test subjects and various experimental types that involve genetic changes. Several sections specifically pertain to human genetic engineering, including Section III-C-1. This section describes required review processes and other aspects when seeking approval to begin clinical research involving genetic transfer into a human patient.[170] The protocol for a gene therapy clinical trial must be approved by the NIH’s Recombinant DNA Advisory Committee prior to any clinical trial beginning; this is different from any other kind of clinical trial.[169]

As with other kinds of drugs, the FDA regulates the quality and safety of gene therapy products and supervises how these products are used clinically. Therapeutic alteration of the human genome falls under the same regulatory requirements as any other medical treatment. Research involving human subjects, such as clinical trials, must be reviewed and approved by the FDA and an Institutional Review Board.[171][172]

Gene therapy is the basis for the plotline of the film I Am Legend[173] and the TV show Will Gene Therapy Change the Human Race?.[174] In 1994, gene therapy was a plot element in The Erlenmeyer Flask, The X-Files’ first season finale. It is also used in Stargate as a means of allowing humans to use Ancient technology.[175]

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Gene therapy – Wikipedia

Human Genetic Engineering Effects

Some people can think of Human Genetic Engineering as a thing that makes them live a healthier life for a long time. People can think of it as a something straight from the heaven or a programmed human being. Genetic engineering is a concept that can be used for enhancing the life of human beings.

However, Human Genetic Engineering Effects are also there that can harm humans. A lot of doctors or scientists involved in gene engineering believe that if the research produces accurate and effective manipulation of DNA in the humans, then they can make medicines for diseases that have no cure. This will also enable the doctors to make changes in the genes of a child before the birth of that child, so there will be no defects on a child from birth.

This process can also be applied on curing hereditary disease. It will prevent the disease from carrying forward to other coming generations. This research primarily focused on being applied on families that have a history of suffering from diseases. It will fix the wrong positioning of the genes. TheHuman Genetic Engineering Effects are in its application towards animals and plants that have been modified genetically. When farmers make use of gene-engineering for breeding plants, then this will result in fast production of food items. Fast and increased production will also put down the prices of several food items. Human Genetic Engineering can also add taste and nutrition to different food items.

Human Genetic Engineering Effects can also help in fighting with severe uncured diseases. Those who suffer from life threatening diseases like cancer or AIDS can have a better idea about maintaining their lives according to the circumstances. This can only be done with the help of Human Genetic Engineering.

Hereditary diseases will not trouble any person, and nor there will be any fear of deadly virus taking place in people on all corners of the world. Human Genetic Engineering can achieve all these things in a theoretical way. Human Genetic Engineering Effects can also be seen in societies concerning health. It has tremendous benefits on health.

Human Genetic Engineering can help people in fighting with cystic fibrosis problems. It also helps to fight against diabetes, and many other specific diseases. Bubble boy is also a disease that can be treated successfully with the help Human Genetic Engineering. It is also termed as Severe Combined Immune efficiency.

Gene mutation is the only thing responsible for the characterization of this deadly disease. This mutation causes ADA deficiencies that later result in destroying the immune system cells. Human Genetic Engineering Effects include ecological problems that might be present in organisms developed or generated by Human Genetic Engineering. However, it can leave positive impacts on a lot of diseases.

One cannot predict the changes that can occur with the use of species that generates with the help of Human Genetic Engineering Effects. A newly generated species creates ecology imbalances due to Human Genetic Engineering Effects. This is a similar case with exotic or natural species.

Human Genetic Engineering Effects

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Human Genetic Engineering Effects

Human Genetic Engineering Pros And Cons

Many human genetic engineering pros and cons are there that have stayed the same since its introduction to humanity. When the humans started harnessing the atomic powers, then just few years later they also start recognizing the effects of human genetic engineering on mankind. Many scientists have a belief that gene therapy can be a mainstream for saving lives of many people. A lot of human genetic engineering pros and cons have been involved since the evolution of genetic engineering. Mentioned below are some important advantages or pros of genetic engineering:

Other human genetic engineering pros and cons include the desirable characteristics in different plants and animals at the same time convenient. One can also do the manipulation of genes in trees or big plants. This will enable the trees to absorb increased amount of carbon dioxide, and it will reduce the effects of global warming. However, there is a question from critics that whether man has the right to do such manipulations or alterations in the genes of natural things.

With human genetic engineering, there is always a chance for altering the wheat plants genetics, which will then enable it to grow insulin. Human genetic engineering pros and cons have been among the concern of a lot of people involved in genetic engineering. Likewise the pros, certain cons are there of using the genetic engineering. Mentioned below are the cons of human genetic engineering:

The evolution of genetic engineering gets the consideration of being the biggest breakthroughs in the history of mankind after the evolution of atomic energy, and few other scientific discoveries. However, human genetic engineering pros and cons together have contributed a lot in creating a controversial image of it among the people.

All these eventualities have forced the government of many countries to make strict legislation laws to put restrictions on different experiment being made on human genetic engineering. They have made this decision by considering different human genetic engineering pros and cons.

Human Genetic Engineering Pros And Cons

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Human Genetic Engineering Pros And Cons

Human or Superhuman? – National Catholic Register

Church Teaching on Genetic Engineering: May 6 issue column.

Human genetic engineering has always been the stuff of science-fiction novels and blockbuster Hollywood films. Except that it is no longer confined to books and movies.

Scientists and doctors are already attempting to genetically alter human beings and our cells. And whether you realize it or not, you and your children are being bombarded in popular media with mixed messages on the ethics surrounding human genetic engineering.

So what does the Church say about the genetic engineering of humans?

The majority of Catholics would likely say that the Church opposes any genetic modification in humans. But that is not what our Church teaches. Actually, the Church does support human genetic engineering; it just has to be the right kind.

Surprised? Most Catholics probably are.

To understand Catholic Church teaching on genetic engineering, it is critical to understand an important distinction under the umbrella of genetic engineering: the difference between therapy and enhancement. It is a distinction that every Catholic should learn to identify, both in the real world and in fiction. Gene therapy and genetic enhancement are technically both genetic engineering, but there are important moral differences.

For decades, researchers have worked toward using genetic modification called gene therapy to cure devastating genetic diseases. Gene therapy delivers a copy of a normal gene into the cells of a patient in an attempt to correct a defective gene. This genetic alteration would then cure or slow the progress of that disease. In many cases, the added gene would produce a protein that is missing or not functioning in a patient because of a genetic mutation.

One of the best examples where researchers hope gene therapy will be able to treat genetic disease is Duchenne Muscular Dystrophy or DMD. DMD is an inherited disorder where a patient cannot make dystrophin, a protein that supports muscle tissue. DMD strikes in early childhood and slowly degrades all muscle tissue, including heart muscle. The average life expectancy of someone with DMD is only 30 years.

Over the last few years, researchers have been studying mice with DMD. They have been successful in inserting the normal dystrophin gene into the DNA of the mice. These genetically engineered mice were then able to produce eight times more dystrophin than mice with DMD. More dystrophin means more muscle, which, in the case of a devastating muscle-wasting disease like DMD, would be a lifesaver.

Almost immediately after the announcement of this breakthrough, the researchers were inundated with calls from bodybuilders and athletes who wanted to be genetically modified to make more muscle.

The callers essentially wanted to take the genetic engineering designed to treat a fatal disease and apply it to their already healthy bodies.

Genetically engineering a normal man who wants more muscle to improve his athletic ability is no longer gene therapy. Instead, it is genetic enhancement.

Genetic enhancement would take an otherwise healthy person and genetically modify him to be more than human, not just in strength, but also in intelligence, beauty or any other desirable trait.

So why is the distinction between gene therapy and genetic enhancement important? The Catholic Church is clear that gene therapy is good, while genetic enhancement is morally wrong.

Why? Because gene therapy seeks to return a patient to normal human functioning. Genetic enhancement, on the other hand, assumes that mans normal state is flawed and lacking, that mans natural biology needs enhancing. Genetic enhancement would intentionally and fundamentally alter a human being in ways not possible by nature, which means in ways God never intended.

The goal of medical intervention must always be the natural development of a human being, respecting the patients inherent dignity and worth. Enhancement destroys that inherent dignity by completely rejecting mankinds natural biology. From the Charter for Health Care Workers by the Pontifical Council for Pastoral Assistance:

In moral evaluation, a distinction must be made between strictly therapeutic manipulation, which aims to cure illnesses caused by genetic or chromosome anomalies (genetic therapy), and manipulation, altering the human genetic patrimony. A curative intervention, which is also called genetic surgery, will be considered desirable in principle, provided its purpose is the real promotion of the personal well-being of the individual, without damaging his integrity or worsening his condition of life.

On the other hand, interventions which are not directly curative, the purpose of which is the production of human beings selected according to sex or other predetermined qualities, which change the genotype of the individual and of the human species, are contrary to the personal dignity of the human being, to his integrity and to his identity. Therefore, they can be in no way justified on the pretext that they will produce some beneficial results for humanity in the future. No social or scientific usefulness and no ideological purpose could ever justify an intervention on the human genome unless it be therapeutic; that is, its finality must be the natural development of the human being.

So genetic engineering to cure or treat disease or disability is good.

Genetic engineering to change the fundamental nature of mankind, to take an otherwise healthy person and engineer him to be more than human is bad.

There is much misinformation surrounding the Catholic Churchs teaching on human genetic engineering. One example is in a piece in The New York Times by David Frum. Frum states that John Paul II supported genetic enhancement and, therefore, the Church does as well. Frum performs a sleight of hand, whether intentional or not. See if you can spot it:

The anti-abortion instincts of many conservatives naturally incline them to look at such [genetic engineering] techniques with suspicion and, indeed, it is certainly easy to imagine how they might be abused. Yet in an important address delivered as long ago as 1983, Pope John Paul II argued that genetic enhancement was permissible indeed, laudable even from a Catholic point of view, as long as it met certain basic moral rules. Among those rules: that these therapies be available to all.

Frum discusses enhancement and therapy as if they are the same. He equates them using the words therapies and enhancement interchangeably. Because John Paul II praised gene therapy, the assumption was that he must laud genetic enhancement as well. This confusion is common because, many argue, there is not a technical difference between therapy and enhancement, so lumping them together is acceptable.

Catholics must not fall into this trap. Philosophically, gene therapy and genetic enhancement are different. One seeks to return normal functioning; the other seeks to take normal functioning and alter it to be abnormal.

There are practical differences between therapy and enhancement as well. Genetic engineering has already had unintended consequences and unforeseen side effects. Gene-therapy trials to cure disease in humans have been going on for decades. All has not gone as planned. Some patients have developed cancer as a result of these attempts at genetically altering their cells.

In 1999, a boy named Jesse Gelsinger was injected with a virus designed to deliver a gene to treat a genetic liver disease. Jesse could have continued with his current treatment regime of medication, but he wanted to help others with the same disorder, so he enrolled in the trial. Tragically, Jesse died four days later from the gene therapy he received.

In 2007, 36-year-old mother Jolee Mohr died while participating in a gene-therapy trial. She had rheumatoid arthritis, and just after the gene therapy (also using a virus for delivery) was injected into her knee, she developed a sudden infection that caused organ failure. An investigation concluded that her death was likely not a direct result of the gene therapy, but some experts think that with something as treatable as rheumatoid arthritis she should never have been entered into such a trial. They argued that, because of the risks, gene therapy should only be used for treating life-threatening illness.

In other words, genetic engineering should only be tried in cases where the benefits will outweigh the risks, as in the treatment of life-threatening conditions. Currently, gene therapy is being undertaken because the risk of the genetic engineering is outweighed by the devastation of the disease it is attempting to cure. With the risks inherent in genetic modification, it should never be attempted on an otherwise healthy person.

You may be thinking that such risky enhancement experiments would never happen. Scientists and doctors would never attempt genetic modifications in healthy humans; human enhancements only exist in science fiction and will stay there. Except science and academia are already looking into it.

The National Institutes of Health (NIH) has awarded Maxwell Mehlman, director of the Law-Medicine Center at Case Western Reserve University School of Law, $773,000 to develop standards for tests on human subjects in genetic-enhancement research. Research that would take otherwise normal humans and make them smarter, stronger or better-looking. If the existing human-trial standards cannot meet the ethical conditions needed for genetic-enhancement research, Mehlman has been asked to recommend changes.

In a recent paper in the journal Ethics, Policy & Environment, S. Matthew Liao, a professor of philosophy and bioethics at New York University, explored ways humanity can change its nature to combat climate change. One of the suggestions Liao discusses is to genetically engineer human eyes to be like cat eyes so we can all see in the dark. This would reduce the need for lighting and reduce energy usage. Liao also discusses genetically modifying our offspring to be smaller so they eat less and use fewer resources.

Of course, Liao insists these are just discussions of possibilities, but what begins as discussions among academics often becomes common among the masses.

Once gene therapy has been perfected and becomes a mainstream treatment for genetic disease, the cries for genetic enhancement will be deafening. The masses will scream that they can do to their bodies as they wish and they wish to no longer be simply human. They wish to be super human.

And with conscience clauses for medical professionals under attack, doctors and nurses may be unable to morally object to genetically altering their perfectly healthy patient or a parents perfectly healthy child.

It is important for Catholics to not turn their backs on technical advancements in biotechnology simply because the advancements are complex.

We can still influence the public consciousness when it comes to human genetic engineering. We are obliged to loudly draw the line between therapy and enhancement otherwise, society, like Frum, will confuse the two.

It is not too late to make sure medically relevant genetic engineering does not turn into engineering that forever changes the nature of man.

Rebecca Taylor is a clinicallaboratory specialist inmolecular biology.She writes about bioethics on her

blog Mary Meets Dolly.

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Human or Superhuman? – National Catholic Register

Gene therapy – Wikipedia

In the medicine field, gene therapy (also called human gene transfer) is the therapeutic delivery of nucleic acid into a patient’s cells as a drug to treat disease.[1][2] The first attempt at modifying human DNA was performed in 1980 by Martin Cline, but the first successful nuclear gene transfer in humans, approved by the National Institutes of Health, was performed in May 1989.[3] The first therapeutic use of gene transfer as well as the first direct insertion of human DNA into the nuclear genome was performed by French Anderson in a trial starting in September 1990.

Between 1989 and February 2016, over 2,300 clinical trials had been conducted, more than half of them in phase I.[4]

Not all medical procedures that introduce alterations to a patient’s genetic makeup can be considered gene therapy. Bone marrow transplantation and organ transplants in general have been found to introduce foreign DNA into patients.[5] Gene therapy is defined by the precision of the procedure and the intention of direct therapeutic effects.

Gene therapy was conceptualized in 1972, by authors who urged caution before commencing human gene therapy studies.

The first attempt, an unsuccessful one, at gene therapy (as well as the first case of medical transfer of foreign genes into humans not counting organ transplantation) was performed by Martin Cline on 10 July 1980.[6][7] Cline claimed that one of the genes in his patients was active six months later, though he never published this data or had it verified[8] and even if he is correct, it’s unlikely it produced any significant beneficial effects treating beta-thalassemia.

After extensive research on animals throughout the 1980s and a 1989 bacterial gene tagging trial on humans, the first gene therapy widely accepted as a success was demonstrated in a trial that started on 14 September 1990, when Ashi DeSilva was treated for ADA-SCID.[9]

The first somatic treatment that produced a permanent genetic change was performed in 1993.[citation needed]

Gene therapy is a way to fix a genetic problem at its source. The polymers are either translated into proteins, interfere with target gene expression, or possibly correct genetic mutations.

The most common form uses DNA that encodes a functional, therapeutic gene to replace a mutated gene. The polymer molecule is packaged within a “vector”, which carries the molecule inside cells.

Early clinical failures led to dismissals of gene therapy. Clinical successes since 2006 regained researchers’ attention, although as of 2014, it was still largely an experimental technique.[10] These include treatment of retinal diseases Leber’s congenital amaurosis[11][12][13][14] and choroideremia,[15] X-linked SCID,[16] ADA-SCID,[17][18] adrenoleukodystrophy,[19] chronic lymphocytic leukemia (CLL),[20] acute lymphocytic leukemia (ALL),[21] multiple myeloma,[22] haemophilia,[18] and Parkinson’s disease.[23] Between 2013 and April 2014, US companies invested over $600 million in the field.[24]

The first commercial gene therapy, Gendicine, was approved in China in 2003 for the treatment of certain cancers.[25] In 2011 Neovasculgen was registered in Russia as the first-in-class gene-therapy drug for treatment of peripheral artery disease, including critical limb ischemia.[26] In 2012 Glybera, a treatment for a rare inherited disorder, became the first treatment to be approved for clinical use in either Europe or the United States after its endorsement by the European Commission.[10][27]

Following early advances in genetic engineering of bacteria, cells, and small animals, scientists started considering how to apply it to medicine. Two main approaches were considered replacing or disrupting defective genes.[28] Scientists focused on diseases caused by single-gene defects, such as cystic fibrosis, haemophilia, muscular dystrophy, thalassemia, and sickle cell anemia. Glybera treats one such disease, caused by a defect in lipoprotein lipase.[27]

DNA must be administered, reach the damaged cells, enter the cell and either express or disrupt a protein.[29] Multiple delivery techniques have been explored. The initial approach incorporated DNA into an engineered virus to deliver the DNA into a chromosome.[30][31] Naked DNA approaches have also been explored, especially in the context of vaccine development.[32]

Generally, efforts focused on administering a gene that causes a needed protein to be expressed. More recently, increased understanding of nuclease function has led to more direct DNA editing, using techniques such as zinc finger nucleases and CRISPR. The vector incorporates genes into chromosomes. The expressed nucleases then knock out and replace genes in the chromosome. As of 2014 these approaches involve removing cells from patients, editing a chromosome and returning the transformed cells to patients.[33]

Gene editing is a potential approach to alter the human genome to treat genetic diseases,[34] viral diseases,[35] and cancer.[36] As of 2016 these approaches were still years from being medicine.[37][38]

Gene therapy may be classified into two types:

In somatic cell gene therapy (SCGT), the therapeutic genes are transferred into any cell other than a gamete, germ cell, gametocyte, or undifferentiated stem cell. Any such modifications affect the individual patient only, and are not inherited by offspring. Somatic gene therapy represents mainstream basic and clinical research, in which therapeutic DNA (either integrated in the genome or as an external episome or plasmid) is used to treat disease.

Over 600 clinical trials utilizing SCGT are underway in the US. Most focus on severe genetic disorders, including immunodeficiencies, haemophilia, thalassaemia, and cystic fibrosis. Such single gene disorders are good candidates for somatic cell therapy. The complete correction of a genetic disorder or the replacement of multiple genes is not yet possible. Only a few of the trials are in the advanced stages.[39]

In germline gene therapy (GGT), germ cells (sperm or egg cells) are modified by the introduction of functional genes into their genomes. Modifying a germ cell causes all the organism’s cells to contain the modified gene. The change is therefore heritable and passed on to later generations. Australia, Canada, Germany, Israel, Switzerland, and the Netherlands[40] prohibit GGT for application in human beings, for technical and ethical reasons, including insufficient knowledge about possible risks to future generations[40] and higher risks versus SCGT.[41] The US has no federal controls specifically addressing human genetic modification (beyond FDA regulations for therapies in general).[40][42][43][44]

The delivery of DNA into cells can be accomplished by multiple methods. The two major classes are recombinant viruses (sometimes called biological nanoparticles or viral vectors) and naked DNA or DNA complexes (non-viral methods).

In order to replicate, viruses introduce their genetic material into the host cell, tricking the host’s cellular machinery into using it as blueprints for viral proteins. Retroviruses go a stage further by having their genetic material copied into the genome of the host cell. Scientists exploit this by substituting a virus’s genetic material with therapeutic DNA. (The term ‘DNA’ may be an oversimplification, as some viruses contain RNA, and gene therapy could take this form as well.) A number of viruses have been used for human gene therapy, including retroviruses, adenoviruses, herpes simplex, vaccinia, and adeno-associated virus.[4] Like the genetic material (DNA or RNA) in viruses, therapeutic DNA can be designed to simply serve as a temporary blueprint that is degraded naturally or (at least theoretically) to enter the host’s genome, becoming a permanent part of the host’s DNA in infected cells.

Non-viral methods present certain advantages over viral methods, such as large scale production and low host immunogenicity. However, non-viral methods initially produced lower levels of transfection and gene expression, and thus lower therapeutic efficacy. Later technology remedied this deficiency.[citation needed]

Methods for non-viral gene therapy include the injection of naked DNA, electroporation, the gene gun, sonoporation, magnetofection, the use of oligonucleotides, lipoplexes, dendrimers, and inorganic nanoparticles.

Some of the unsolved problems include:

Three patients’ deaths have been reported in gene therapy trials, putting the field under close scrutiny. The first was that of Jesse Gelsinger in 1999. Jesse Gelsinger died because of immune rejection response.[51] One X-SCID patient died of leukemia in 2003.[9] In 2007, a rheumatoid arthritis patient died from an infection; the subsequent investigation concluded that the death was not related to gene therapy.[52]

In 1972 Friedmann and Roblin authored a paper in Science titled “Gene therapy for human genetic disease?”[53] Rogers (1970) was cited for proposing that exogenous good DNA be used to replace the defective DNA in those who suffer from genetic defects.[54]

In 1984 a retrovirus vector system was designed that could efficiently insert foreign genes into mammalian chromosomes.[55]

The first approved gene therapy clinical research in the US took place on 14 September 1990, at the National Institutes of Health (NIH), under the direction of William French Anderson.[56] Four-year-old Ashanti DeSilva received treatment for a genetic defect that left her with ADA-SCID, a severe immune system deficiency. The defective gene of the patient’s blood cells was replaced by the functional variant. Ashantis immune system was partially restored by the therapy. Production of the missing enzyme was temporarily stimulated, but the new cells with functional genes were not generated. She led a normal life only with the regular injections performed every two months. The effects were successful, but temporary.[57]

Cancer gene therapy was introduced in 1992/93 (Trojan et al. 1993).[58] The treatment of glioblastoma multiforme, the malignant brain tumor whose outcome is always fatal, was done using a vector expressing antisense IGF-I RNA (clinical trial approved by NIH protocolno.1602 November 24, 1993,[59] and by the FDA in 1994). This therapy also represents the beginning of cancer immunogene therapy, a treatment which proves to be effective due to the anti-tumor mechanism of IGF-I antisense, which is related to strong immune and apoptotic phenomena.

In 1992 Claudio Bordignon, working at the Vita-Salute San Raffaele University, performed the first gene therapy procedure using hematopoietic stem cells as vectors to deliver genes intended to correct hereditary diseases.[60] In 2002 this work led to the publication of the first successful gene therapy treatment for adenosine deaminase deficiency (ADA-SCID). The success of a multi-center trial for treating children with SCID (severe combined immune deficiency or “bubble boy” disease) from 2000 and 2002, was questioned when two of the ten children treated at the trial’s Paris center developed a leukemia-like condition. Clinical trials were halted temporarily in 2002, but resumed after regulatory review of the protocol in the US, the United Kingdom, France, Italy, and Germany.[61]

In 1993 Andrew Gobea was born with SCID following prenatal genetic screening. Blood was removed from his mother’s placenta and umbilical cord immediately after birth, to acquire stem cells. The allele that codes for adenosine deaminase (ADA) was obtained and inserted into a retrovirus. Retroviruses and stem cells were mixed, after which the viruses inserted the gene into the stem cell chromosomes. Stem cells containing the working ADA gene were injected into Andrew’s blood. Injections of the ADA enzyme were also given weekly. For four years T cells (white blood cells), produced by stem cells, made ADA enzymes using the ADA gene. After four years more treatment was needed.[62]

Jesse Gelsinger’s death in 1999 impeded gene therapy research in the US.[63][64] As a result, the FDA suspended several clinical trials pending the reevaluation of ethical and procedural practices.[65]

The modified cancer gene therapy strategy of antisense IGF-I RNA (NIH n 1602)[59] using antisense / triple helix anti-IGF-I approach was registered in 2002 by Wiley gene therapy clinical trial – n 635 and 636. The approach has shown promising results in the treatment of six different malignant tumors: glioblastoma, cancers of liver, colon, prostate, uterus, and ovary (Collaborative NATO Science Programme on Gene Therapy USA, France, Poland n LST 980517 conducted by J. Trojan) (Trojan et al., 2012). This anti-gene antisense/triple helix therapy has proven to be efficient, due to the mechanism stopping simultaneously IGF-I expression on translation and transcription levels, strengthening anti-tumor immune and apoptotic phenomena.

Sickle-cell disease can be treated in mice.[66] The mice which have essentially the same defect that causes human cases used a viral vector to induce production of fetal hemoglobin (HbF), which normally ceases to be produced shortly after birth. In humans, the use of hydroxyurea to stimulate the production of HbF temporarily alleviates sickle cell symptoms. The researchers demonstrated this treatment to be a more permanent means to increase therapeutic HbF production.[67]

A new gene therapy approach repaired errors in messenger RNA derived from defective genes. This technique has the potential to treat thalassaemia, cystic fibrosis and some cancers.[68]

Researchers created liposomes 25 nanometers across that can carry therapeutic DNA through pores in the nuclear membrane.[69]

In 2003 a research team inserted genes into the brain for the first time. They used liposomes coated in a polymer called polyethylene glycol, which unlike viral vectors, are small enough to cross the bloodbrain barrier.[70]

Short pieces of double-stranded RNA (short, interfering RNAs or siRNAs) are used by cells to degrade RNA of a particular sequence. If a siRNA is designed to match the RNA copied from a faulty gene, then the abnormal protein product of that gene will not be produced.[71]

Gendicine is a cancer gene therapy that delivers the tumor suppressor gene p53 using an engineered adenovirus. In 2003, it was approved in China for the treatment of head and neck squamous cell carcinoma.[25]

In March researchers announced the successful use of gene therapy to treat two adult patients for X-linked chronic granulomatous disease, a disease which affects myeloid cells and damages the immune system. The study is the first to show that gene therapy can treat the myeloid system.[72]

In May a team reported a way to prevent the immune system from rejecting a newly delivered gene.[73] Similar to organ transplantation, gene therapy has been plagued by this problem. The immune system normally recognizes the new gene as foreign and rejects the cells carrying it. The research utilized a newly uncovered network of genes regulated by molecules known as microRNAs. This natural function selectively obscured their therapeutic gene in immune system cells and protected it from discovery. Mice infected with the gene containing an immune-cell microRNA target sequence did not reject the gene.

In August scientists successfully treated metastatic melanoma in two patients using killer T cells genetically retargeted to attack the cancer cells.[74]

In November researchers reported on the use of VRX496, a gene-based immunotherapy for the treatment of HIV that uses a lentiviral vector to deliver an antisense gene against the HIV envelope. In a phase I clinical trial, five subjects with chronic HIV infection who had failed to respond to at least two antiretroviral regimens were treated. A single intravenous infusion of autologous CD4 T cells genetically modified with VRX496 was well tolerated. All patients had stable or decreased viral load; four of the five patients had stable or increased CD4 T cell counts. All five patients had stable or increased immune response to HIV antigens and other pathogens. This was the first evaluation of a lentiviral vector administered in a US human clinical trial.[75][76]

In May researchers announced the first gene therapy trial for inherited retinal disease. The first operation was carried out on a 23-year-old British male, Robert Johnson, in early 2007.[77]

Leber’s congenital amaurosis is an inherited blinding disease caused by mutations in the RPE65 gene. The results of a small clinical trial in children were published in April.[11] Delivery of recombinant adeno-associated virus (AAV) carrying RPE65 yielded positive results. In May two more groups reported positive results in independent clinical trials using gene therapy to treat the condition. In all three clinical trials, patients recovered functional vision without apparent side-effects.[11][12][13][14]

In September researchers were able to give trichromatic vision to squirrel monkeys.[78] In November 2009, researchers halted a fatal genetic disorder called adrenoleukodystrophy in two children using a lentivirus vector to deliver a functioning version of ABCD1, the gene that is mutated in the disorder.[79]

An April paper reported that gene therapy addressed achromatopsia (color blindness) in dogs by targeting cone photoreceptors. Cone function and day vision were restored for at least 33 months in two young specimens. The therapy was less efficient for older dogs.[80]

In September it was announced that an 18-year-old male patient in France with beta-thalassemia major had been successfully treated.[81] Beta-thalassemia major is an inherited blood disease in which beta haemoglobin is missing and patients are dependent on regular lifelong blood transfusions.[82] The technique used a lentiviral vector to transduce the human -globin gene into purified blood and marrow cells obtained from the patient in June 2007.[83] The patient’s haemoglobin levels were stable at 9 to 10 g/dL. About a third of the hemoglobin contained the form introduced by the viral vector and blood transfusions were not needed.[83][84] Further clinical trials were planned.[85] Bone marrow transplants are the only cure for thalassemia, but 75% of patients do not find a matching donor.[84]

Cancer immunogene therapy using modified antigene, antisense/triple helix approach was introduced in South America in 2010/11 in La Sabana University, Bogota (Ethical Committee 14 December 2010, no P-004-10). Considering the ethical aspect of gene diagnostic and gene therapy targeting IGF-I, the IGF-I expressing tumors i.e. lung and epidermis cancers were treated (Trojan et al. 2016).[86][87]

In 2007 and 2008, a man (Timothy Ray Brown) was cured of HIV by repeated hematopoietic stem cell transplantation (see also allogeneic stem cell transplantation, allogeneic bone marrow transplantation, allotransplantation) with double-delta-32 mutation which disables the CCR5 receptor. This cure was accepted by the medical community in 2011.[88] It required complete ablation of existing bone marrow, which is very debilitating.

In August two of three subjects of a pilot study were confirmed to have been cured from chronic lymphocytic leukemia (CLL). The therapy used genetically modified T cells to attack cells that expressed the CD19 protein to fight the disease.[20] In 2013, the researchers announced that 26 of 59 patients had achieved complete remission and the original patient had remained tumor-free.[89]

Human HGF plasmid DNA therapy of cardiomyocytes is being examined as a potential treatment for coronary artery disease as well as treatment for the damage that occurs to the heart after myocardial infarction.[90][91]

In 2011 Neovasculgen was registered in Russia as the first-in-class gene-therapy drug for treatment of peripheral artery disease, including critical limb ischemia; it delivers the gene encoding for VEGF.[92][26] Neovasculogen is a plasmid encoding the CMV promoter and the 165 amino acid form of VEGF.[93][94]

The FDA approved Phase 1 clinical trials on thalassemia major patients in the US for 10 participants in July.[95] The study was expected to continue until 2015.[85]

In July 2012, the European Medicines Agency recommended approval of a gene therapy treatment for the first time in either Europe or the United States. The treatment used Alipogene tiparvovec (Glybera) to compensate for lipoprotein lipase deficiency, which can cause severe pancreatitis.[96] The recommendation was endorsed by the European Commission in November 2012[10][27][97][98] and commercial rollout began in late 2014.[99] Alipogene tiparvovec was expected to cost around $1.6 million per treatment in 2012,[100] revised to $1 million in 2015,[101] making it the most expensive medicine in the world at the time.[102] As of 2016, only one person had been treated with drug.[103]

In December 2012, it was reported that 10 of 13 patients with multiple myeloma were in remission “or very close to it” three months after being injected with a treatment involving genetically engineered T cells to target proteins NY-ESO-1 and LAGE-1, which exist only on cancerous myeloma cells.[22]

In March researchers reported that three of five adult subjects who had acute lymphocytic leukemia (ALL) had been in remission for five months to two years after being treated with genetically modified T cells which attacked cells with CD19 genes on their surface, i.e. all B-cells, cancerous or not. The researchers believed that the patients’ immune systems would make normal T-cells and B-cells after a couple of months. They were also given bone marrow. One patient relapsed and died and one died of a blood clot unrelated to the disease.[21]

Following encouraging Phase 1 trials, in April, researchers announced they were starting Phase 2 clinical trials (called CUPID2 and SERCA-LVAD) on 250 patients[104] at several hospitals to combat heart disease. The therapy was designed to increase the levels of SERCA2, a protein in heart muscles, improving muscle function.[105] The FDA granted this a Breakthrough Therapy Designation to accelerate the trial and approval process.[106] In 2016 it was reported that no improvement was found from the CUPID 2 trial.[107]

In July researchers reported promising results for six children with two severe hereditary diseases had been treated with a partially deactivated lentivirus to replace a faulty gene and after 732 months. Three of the children had metachromatic leukodystrophy, which causes children to lose cognitive and motor skills.[108] The other children had Wiskott-Aldrich syndrome, which leaves them to open to infection, autoimmune diseases, and cancer.[109] Follow up trials with gene therapy on another six children with Wiskott-Aldrich syndrome were also reported as promising.[110][111]

In October researchers reported that two children born with adenosine deaminase severe combined immunodeficiency disease (ADA-SCID) had been treated with genetically engineered stem cells 18 months previously and that their immune systems were showing signs of full recovery. Another three children were making progress.[18] In 2014 a further 18 children with ADA-SCID were cured by gene therapy.[112] ADA-SCID children have no functioning immune system and are sometimes known as “bubble children.”[18]

Also in October researchers reported that they had treated six hemophilia sufferers in early 2011 using an adeno-associated virus. Over two years later all six were producing clotting factor.[18][113]

In January researchers reported that six choroideremia patients had been treated with adeno-associated virus with a copy of REP1. Over a six-month to two-year period all had improved their sight.[114][115] By 2016, 32 patients had been treated with positive results and researchers were hopeful the treatment would be long-lasting.[15] Choroideremia is an inherited genetic eye disease with no approved treatment, leading to loss of sight.

In March researchers reported that 12 HIV patients had been treated since 2009 in a trial with a genetically engineered virus with a rare mutation (CCR5 deficiency) known to protect against HIV with promising results.[116][117]

Clinical trials of gene therapy for sickle cell disease were started in 2014.[118][119] There is a need for high quality randomised controlled trials assessing the risks and benefits involved with gene therapy for people with sickle cell disease.[120]

In February LentiGlobin BB305, a gene therapy treatment undergoing clinical trials for treatment of beta thalassemia gained FDA “breakthrough” status after several patients were able to forgo the frequent blood transfusions usually required to treat the disease.[121]

In March researchers delivered a recombinant gene encoding a broadly neutralizing antibody into monkeys infected with simian HIV; the monkeys’ cells produced the antibody, which cleared them of HIV. The technique is named immunoprophylaxis by gene transfer (IGT). Animal tests for antibodies to ebola, malaria, influenza, and hepatitis were underway.[122][123]

In March, scientists, including an inventor of CRISPR, Jennifer Doudna, urged a worldwide moratorium on germline gene therapy, writing “scientists should avoid even attempting, in lax jurisdictions, germline genome modification for clinical application in humans” until the full implications “are discussed among scientific and governmental organizations”.[124][125][126][127]

In October, researchers announced that they had treated a baby girl, Layla Richards, with an experimental treatment using donor T-cells genetically engineered using TALEN to attack cancer cells. One year after the treatment she was still free of her cancer (a highly aggressive form of acute lymphoblastic leukaemia [ALL]).[128] Children with highly aggressive ALL normally have a very poor prognosis and Layla’s disease had been regarded as terminal before the treatment.[129]

In December, scientists of major world academies called for a moratorium on inheritable human genome edits, including those related to CRISPR-Cas9 technologies[130] but that basic research including embryo gene editing should continue.[131]

In April the Committee for Medicinal Products for Human Use of the European Medicines Agency endorsed a gene therapy treatment called Strimvelis[132][133] and the European Commission approved it in June.[134] This treats children born with adenosine deaminase deficiency and who have no functioning immune system. This was the second gene therapy treatment to be approved in Europe.[135]

In October, Chinese scientists reported they had started a trial to genetically modify T-cells from 10 adult patients with lung cancer and reinject the modified T-cells back into their bodies to attack the cancer cells. The T-cells had the PD-1 protein (which stops or slows the immune response) removed using CRISPR-Cas9.[136][137]

A 2016 Cochrane systematic review looking at data from four trials on topical cystic fibrosis transmembrane conductance regulator (CFTR) gene therapy does not support its clinical use as a mist inhaled into the lungs to treat cystic fibrosis patients with lung infections. One of the four trials did find weak evidence that liposome-based CFTR gene transfer therapy may lead to a small respiratory improvement for people with CF. This weak evidence is not enough to make a clinical recommendation for routine CFTR gene therapy.[138]

In February Kite Pharma announced results from a clinical trial of CAR-T cells in around a hundred people with advanced Non-Hodgkin lymphoma.[139]

In March, French scientists reported on clinical research of gene therapy to treat sickle-cell disease.[140]

In August, the FDA approved tisagenlecleucel for acute lymphoblastic leukemia.[141] Tisagenlecleucel is an adoptive cell transfer therapy for B-cell acute lymphoblastic leukemia; T cells from a person with cancer are removed, genetically engineered to make a specific T-cell receptor (a chimeric T cell receptor, or “CAR-T”) that reacts to the cancer, and are administered back to the person. The T cells are engineered to target a protein called CD19 that is common on B cells. This is the first form of gene therapy to be approved in the United States. In October, a similar therapy called axicabtagene ciloleucel was approved for non-Hodgkin lymphoma.[142]

In December the results of using an adeno-associated virus with blood clotting factor VIII to treat nine haemophilia A patients were published. Six of the seven patients on the high dose regime increased the level of the blood clotting VIII to normal levels. The low and medium dose regimes had no effect on the patient’s blood clotting levels.[143][144]

In December, the FDA approved Luxturna, the first in vivo gene therapy, for the treatment of blindness due to Leber’s congenital amaurosis.[145] The price of this treatment was 850,000 US dollars for both eyes.[146][147] CRISPR gene editing technology has also been used on mice to treat deafness due to the DFNA36 mutation, which also affects humans.[148]

Speculated uses for gene therapy include:

Gene Therapy techniques have the potential to provide alternative treatments for those with infertility. Recently, successful experimentation on mice has proven that fertility can be restored by using the gene therapy method, CRISPR.[149] Spermatogenical stem cells from another organism were transplanted into the testes of an infertile male mouse. The stem cells re-established spermatogenesis and fertility.[150]

Athletes might adopt gene therapy technologies to improve their performance.[151] Gene doping is not known to occur, but multiple gene therapies may have such effects. Kayser et al. argue that gene doping could level the playing field if all athletes receive equal access. Critics claim that any therapeutic intervention for non-therapeutic/enhancement purposes compromises the ethical foundations of medicine and sports.[152]

Genetic engineering could be used to cure diseases, but also to change physical appearance, metabolism, and even improve physical capabilities and mental faculties such as memory and intelligence. Ethical claims about germline engineering include beliefs that every fetus has a right to remain genetically unmodified, that parents hold the right to genetically modify their offspring, and that every child has the right to be born free of preventable diseases.[153][154][155] For parents, genetic engineering could be seen as another child enhancement technique to add to diet, exercise, education, training, cosmetics, and plastic surgery.[156][157] Another theorist claims that moral concerns limit but do not prohibit germline engineering.[158]

Possible regulatory schemes include a complete ban, provision to everyone, or professional self-regulation. The American Medical Associations Council on Ethical and Judicial Affairs stated that “genetic interventions to enhance traits should be considered permissible only in severely restricted situations: (1) clear and meaningful benefits to the fetus or child; (2) no trade-off with other characteristics or traits; and (3) equal access to the genetic technology, irrespective of income or other socioeconomic characteristics.”[159]

As early in the history of biotechnology as 1990, there have been scientists opposed to attempts to modify the human germline using these new tools,[160] and such concerns have continued as technology progressed.[161][162] With the advent of new techniques like CRISPR, in March 2015 a group of scientists urged a worldwide moratorium on clinical use of gene editing technologies to edit the human genome in a way that can be inherited.[124][125][126][127] In April 2015, researchers sparked controversy when they reported results of basic research to edit the DNA of non-viable human embryos using CRISPR.[149][163] A committee of the American National Academy of Sciences and National Academy of Medicine gave qualified support to human genome editing in 2017[164][165] once answers have been found to safety and efficiency problems “but only for serious conditions under stringent oversight.”[166]

Regulations covering genetic modification are part of general guidelines about human-involved biomedical research. There are no international treaties which are legally binding in this area, but there are recommendations for national laws from various bodies.

The Helsinki Declaration (Ethical Principles for Medical Research Involving Human Subjects) was amended by the World Medical Association’s General Assembly in 2008. This document provides principles physicians and researchers must consider when involving humans as research subjects. The Statement on Gene Therapy Research initiated by the Human Genome Organization (HUGO) in 2001 provides a legal baseline for all countries. HUGOs document emphasizes human freedom and adherence to human rights, and offers recommendations for somatic gene therapy, including the importance of recognizing public concerns about such research.[167]

No federal legislation lays out protocols or restrictions about human genetic engineering. This subject is governed by overlapping regulations from local and federal agencies, including the Department of Health and Human Services, the FDA and NIH’s Recombinant DNA Advisory Committee. Researchers seeking federal funds for an investigational new drug application, (commonly the case for somatic human genetic engineering,) must obey international and federal guidelines for the protection of human subjects.[168]

NIH serves as the main gene therapy regulator for federally funded research. Privately funded research is advised to follow these regulations. NIH provides funding for research that develops or enhances genetic engineering techniques and to evaluate the ethics and quality in current research. The NIH maintains a mandatory registry of human genetic engineering research protocols that includes all federally funded projects.

An NIH advisory committee published a set of guidelines on gene manipulation.[169] The guidelines discuss lab safety as well as human test subjects and various experimental types that involve genetic changes. Several sections specifically pertain to human genetic engineering, including Section III-C-1. This section describes required review processes and other aspects when seeking approval to begin clinical research involving genetic transfer into a human patient.[170] The protocol for a gene therapy clinical trial must be approved by the NIH’s Recombinant DNA Advisory Committee prior to any clinical trial beginning; this is different from any other kind of clinical trial.[169]

As with other kinds of drugs, the FDA regulates the quality and safety of gene therapy products and supervises how these products are used clinically. Therapeutic alteration of the human genome falls under the same regulatory requirements as any other medical treatment. Research involving human subjects, such as clinical trials, must be reviewed and approved by the FDA and an Institutional Review Board.[171][172]

Gene therapy is the basis for the plotline of the film I Am Legend[173] and the TV show Will Gene Therapy Change the Human Race?.[174] In 1994, gene therapy was a plot element in The Erlenmeyer Flask, The X-Files’ first season finale. It is also used in Stargate as a means of allowing humans to use Ancient technology.[175]

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Gene therapy – Wikipedia

Human Genetic Engineering Effects

Some people can think of Human Genetic Engineering as a thing that makes them live a healthier life for a long time. People can think of it as a something straight from the heaven or a programmed human being. Genetic engineering is a concept that can be used for enhancing the life of human beings.

However, Human Genetic Engineering Effects are also there that can harm humans. A lot of doctors or scientists involved in gene engineering believe that if the research produces accurate and effective manipulation of DNA in the humans, then they can make medicines for diseases that have no cure. This will also enable the doctors to make changes in the genes of a child before the birth of that child, so there will be no defects on a child from birth.

This process can also be applied on curing hereditary disease. It will prevent the disease from carrying forward to other coming generations. This research primarily focused on being applied on families that have a history of suffering from diseases. It will fix the wrong positioning of the genes. TheHuman Genetic Engineering Effects are in its application towards animals and plants that have been modified genetically. When farmers make use of gene-engineering for breeding plants, then this will result in fast production of food items. Fast and increased production will also put down the prices of several food items. Human Genetic Engineering can also add taste and nutrition to different food items.

Human Genetic Engineering Effects can also help in fighting with severe uncured diseases. Those who suffer from life threatening diseases like cancer or AIDS can have a better idea about maintaining their lives according to the circumstances. This can only be done with the help of Human Genetic Engineering.

Hereditary diseases will not trouble any person, and nor there will be any fear of deadly virus taking place in people on all corners of the world. Human Genetic Engineering can achieve all these things in a theoretical way. Human Genetic Engineering Effects can also be seen in societies concerning health. It has tremendous benefits on health.

Human Genetic Engineering can help people in fighting with cystic fibrosis problems. It also helps to fight against diabetes, and many other specific diseases. Bubble boy is also a disease that can be treated successfully with the help Human Genetic Engineering. It is also termed as Severe Combined Immune efficiency.

Gene mutation is the only thing responsible for the characterization of this deadly disease. This mutation causes ADA deficiencies that later result in destroying the immune system cells. Human Genetic Engineering Effects include ecological problems that might be present in organisms developed or generated by Human Genetic Engineering. However, it can leave positive impacts on a lot of diseases.

One cannot predict the changes that can occur with the use of species that generates with the help of Human Genetic Engineering Effects. A newly generated species creates ecology imbalances due to Human Genetic Engineering Effects. This is a similar case with exotic or natural species.

Human Genetic Engineering Effects

3.59 (71.79%) 173 votes

Read the rest here:

Human Genetic Engineering Effects

Human Genetic Engineering Pros And Cons

Many human genetic engineering pros and cons are there that have stayed the same since its introduction to humanity. When the humans started harnessing the atomic powers, then just few years later they also start recognizing the effects of human genetic engineering on mankind. Many scientists have a belief that gene therapy can be a mainstream for saving lives of many people. A lot of human genetic engineering pros and cons have been involved since the evolution of genetic engineering. Mentioned below are some important advantages or pros of genetic engineering:

Other human genetic engineering pros and cons include the desirable characteristics in different plants and animals at the same time convenient. One can also do the manipulation of genes in trees or big plants. This will enable the trees to absorb increased amount of carbon dioxide, and it will reduce the effects of global warming. However, there is a question from critics that whether man has the right to do such manipulations or alterations in the genes of natural things.

With human genetic engineering, there is always a chance for altering the wheat plants genetics, which will then enable it to grow insulin. Human genetic engineering pros and cons have been among the concern of a lot of people involved in genetic engineering. Likewise the pros, certain cons are there of using the genetic engineering. Mentioned below are the cons of human genetic engineering:

The evolution of genetic engineering gets the consideration of being the biggest breakthroughs in the history of mankind after the evolution of atomic energy, and few other scientific discoveries. However, human genetic engineering pros and cons together have contributed a lot in creating a controversial image of it among the people.

All these eventualities have forced the government of many countries to make strict legislation laws to put restrictions on different experiment being made on human genetic engineering. They have made this decision by considering different human genetic engineering pros and cons.

Human Genetic Engineering Pros And Cons

3.12 (62.35%) 3288 votes

Read the original post:

Human Genetic Engineering Pros And Cons

Human Genetic Engineering Effects

Some people can think of Human Genetic Engineering as a thing that makes them live a healthier life for a long time. People can think of it as a something straight from the heaven or a programmed human being. Genetic engineering is a concept that can be used for enhancing the life of human beings.

However, Human Genetic Engineering Effects are also there that can harm humans. A lot of doctors or scientists involved in gene engineering believe that if the research produces accurate and effective manipulation of DNA in the humans, then they can make medicines for diseases that have no cure. This will also enable the doctors to make changes in the genes of a child before the birth of that child, so there will be no defects on a child from birth.

This process can also be applied on curing hereditary disease. It will prevent the disease from carrying forward to other coming generations. This research primarily focused on being applied on families that have a history of suffering from diseases. It will fix the wrong positioning of the genes. TheHuman Genetic Engineering Effects are in its application towards animals and plants that have been modified genetically. When farmers make use of gene-engineering for breeding plants, then this will result in fast production of food items. Fast and increased production will also put down the prices of several food items. Human Genetic Engineering can also add taste and nutrition to different food items.

Human Genetic Engineering Effects can also help in fighting with severe uncured diseases. Those who suffer from life threatening diseases like cancer or AIDS can have a better idea about maintaining their lives according to the circumstances. This can only be done with the help of Human Genetic Engineering.

Hereditary diseases will not trouble any person, and nor there will be any fear of deadly virus taking place in people on all corners of the world. Human Genetic Engineering can achieve all these things in a theoretical way. Human Genetic Engineering Effects can also be seen in societies concerning health. It has tremendous benefits on health.

Human Genetic Engineering can help people in fighting with cystic fibrosis problems. It also helps to fight against diabetes, and many other specific diseases. Bubble boy is also a disease that can be treated successfully with the help Human Genetic Engineering. It is also termed as Severe Combined Immune efficiency.

Gene mutation is the only thing responsible for the characterization of this deadly disease. This mutation causes ADA deficiencies that later result in destroying the immune system cells. Human Genetic Engineering Effects include ecological problems that might be present in organisms developed or generated by Human Genetic Engineering. However, it can leave positive impacts on a lot of diseases.

One cannot predict the changes that can occur with the use of species that generates with the help of Human Genetic Engineering Effects. A newly generated species creates ecology imbalances due to Human Genetic Engineering Effects. This is a similar case with exotic or natural species.

Human Genetic Engineering Effects

3.59 (71.79%) 173 votes

Read more:

Human Genetic Engineering Effects

Human Genetic Engineering Pros And Cons

Many human genetic engineering pros and cons are there that have stayed the same since its introduction to humanity. When the humans started harnessing the atomic powers, then just few years later they also start recognizing the effects of human genetic engineering on mankind. Many scientists have a belief that gene therapy can be a mainstream for saving lives of many people. A lot of human genetic engineering pros and cons have been involved since the evolution of genetic engineering. Mentioned below are some important advantages or pros of genetic engineering:

Other human genetic engineering pros and cons include the desirable characteristics in different plants and animals at the same time convenient. One can also do the manipulation of genes in trees or big plants. This will enable the trees to absorb increased amount of carbon dioxide, and it will reduce the effects of global warming. However, there is a question from critics that whether man has the right to do such manipulations or alterations in the genes of natural things.

With human genetic engineering, there is always a chance for altering the wheat plants genetics, which will then enable it to grow insulin. Human genetic engineering pros and cons have been among the concern of a lot of people involved in genetic engineering. Likewise the pros, certain cons are there of using the genetic engineering. Mentioned below are the cons of human genetic engineering:

The evolution of genetic engineering gets the consideration of being the biggest breakthroughs in the history of mankind after the evolution of atomic energy, and few other scientific discoveries. However, human genetic engineering pros and cons together have contributed a lot in creating a controversial image of it among the people.

All these eventualities have forced the government of many countries to make strict legislation laws to put restrictions on different experiment being made on human genetic engineering. They have made this decision by considering different human genetic engineering pros and cons.

Human Genetic Engineering Pros And Cons

3.12 (62.35%) 3288 votes

Read more:

Human Genetic Engineering Pros And Cons

Genetic engineering in science fiction – Wikipedia

In literature and especially in science fiction, genetic engineering has been used as a theme or a plot device in many stories.[1][2]

In his 1924 essay Daedalus, or Science and the Future, J. B. S. Haldane predicted a day when biologists would invent new algae to feed the world and ectogenetic children would be created and modified using eugenic selection. Aldous Huxley developed these ideas in a satirical direction for his 1932 novel Brave New World, in which ectogenetic embryos were developed in selected environments to create children of an ‘Alpha’, ‘Beta’, or ‘Gamma’ type.[3]

The advent of large-scale genetic engineering has increased its presence in fiction.[4][5] Genetics research consortia, such as the Wellcome Trust Sanger Institute, have felt the need to distinguish genetic engineering fact from fiction in explaining their work to the public,[1] and have explored the role that genetic engineering has played in the public perception of programs, such as the Human Genome Project.[6]

Beyond the usual library catalog classifications,[7] the Wellcome Trust Sanger Institute[1] and the NHGRI[6] have compiled catalogs of literature in various media with genetics and genetic engineering as a theme or plot device. Such compilations are also available at fan sites.[8]

In the 2000 television series Andromeda, the Nietzscheans (Homo sapiens invictus in Latin) are a race of genetically engineered humans who religiously follow the works of Friedrich Nietzsche, social Darwinism and Dawkinite genetic competitiveness. They claim to be physically perfect and are distinguished by bone blades protruding outwards from the wrist area.

In the book 2312 by Kim Stanley Robinson, genetic engineering of humans, plants and animals and how that affects a society spread over the solar system is explored.

In the Animorphs book series, race of aliens known as the Hork-Bajir were engineered by a race known as the Arns. Another race, the Iskhoots, are another example of genetic engineering. The outer body, the Isk, was created by the Yoort, who also modify themselves to be symbotic to the Isk. Also, a being known as the Ellimist has made species such as the Pemalites by this method.

In the 1983 film Anna to the Infinite Power, the main character was one of seven genetically cloned humans created by Anna Zimmerman as a way to groom a perfect person in her image. After her death, her work was carried on by her successor Dr. Henry Jelliff, who had other plans for the project. But in the end we learn that her original genetic creation, Michaela Dupont, has already acquired her creator’s abilities, including how to build a genetic replicator from scratch.

The 1996 video game series Resident Evil involves the creation of genetically engineered viruses which turn humans and animals into organisms such as zombies, the Tyrants or Hunters by a worldwide pharmaceutical company called the Umbrella Corporation.

In the video game series BioShock, most of the enemies in both BioShock and BioShock 2, referred to as “splicers”, as well as the player, gain superpowers and enhance their physical and mental capabilities by means of genetically engineered plasmids, created by use of ADAM stem cells secreted by a species of sea slug.[9]

The novel Beggars in Spain by Nancy Kress and its sequels are widely recognized by science fiction critics as among the most sophisticated fictional treatments of genetic engineering. They portray genetically-engineered characters whose abilities are far greater than those of ordinary humans (e.g. they are effectively immortal and they function without needing to sleep). At issue is what responsibility they have to use their abilities to help “normal” human beings. Kress explores libertarian and more collectivist philosophies, attempting to define the extent of people’s mutual responsibility for each other’s welfare.

In the Battletech science fiction series, the Clans have developed a genetic engineering program for their warriors, consisting of eugenics and the use of artificial wombs.

In The Champion Maker, a novel by Kevin Joseph, a track coach and a teenage phenom stumble upon a dark conspiracy involving genetic engineering while pursuing Olympic gold.

In the CoDominium series, the planet Sauron develops a supersoldier program. The result were the Sauron Cyborgs, and soldiers. The Cyborgs, who made up only a very small part of the population of Sauron, were part highly genetically engineered human, and part machine. Cyborgs held very high status in Sauron society.

Sauron soldiers, who made up the balance of the population, were the result of generations of genetic engineering. The Sauron soldiers had a variety of physical characteristics and abilities that made the soldiers the best in combat and survival in many hostile environments. For instance, their bones were stronger than unmodified humans. Their lungs extract oxygen more efficiently than normal unmodified humans, allowing them to exert themselves without getting short of breath, or function at high altitudes. Sauron soldiers also have the ability to change the focal length of their eyes, so that they can “zoom” in on a distant object, much like an eagle.

The alien Moties also have used genetic engineering.

In the science fiction series Crest of the Stars, the Abh are a race of genetically engineered humans, who continue to practice the technology. All Abh have been adapted to live in zero-gravity environments, with the same features such as beauty, long life, lifelong youthful appearance, blue hair, and a “space sensory organ”.

In the 2000 TV series Dark Angel, the main character Max is one of a group of genetically engineered supersoldiers spliced with feline DNA.

In military science fiction 1993 television series Exosquad, the plot revolves around the conflict between Terrans (baseline humans) and Neosapiens, a race of genetically engineered sentient (and sterile) humanoids, who were originally bred for slave labour but revolted under the leadership of Phaeton and captured the Homeworlds (Earth, Venus and Mars). During the war, various sub-broods of Neosapiens were invented, such as, Neo Megas (intellectually superior to almost any being in the Solar System), Neo Warriors (cross-breeds with various animals) and Neo Lords (the ultimate supersoldiers).

Genetic modification is also found in the 2002 anime series Gundam SEED. It features enhanced humans called Coordinators who were created from ordinary humans through genetic modification.

In Marvel Comics, the 31st century adventurers called the Guardians of the Galaxy are genetically engineered residents of Mercury, Jupiter, and Pluto.

The 1997 film Gattaca deals with the idea of genetic engineering and eugenics as it projects what class relations would look like in a future society after a few generations of the possibility of genetic engineering.

In Marvel Comics, the Inhumans are the result of genetic engineering of early humans by the Kree alien race.

Rather than deliberate engineering, this 2017 novel by British author Steve Turnbull features a plague that carries genetic material across species, causing a wide variety of mutations. Human attempts to control this plague have resulted in a fascist dystopia.

In the Leviathan universe, a group known as the Darwinists use genetically engineered animals as weapons.

The 2000AD strip, Lobster Random features a former soldier-turned-torturer, who has been modified to not feel pain or need to sleep and has a pair of lobster claws grafted to his hips. This state has left him somewhat grouchy.

In Metal Gear Solid, the Genome Army were given gene therapy enhancements.

Also in the series, the Les Enfants Terribles project involved genetic engineering.

The Moreau series by S. Andrew Swann has as the central premise the proliferation of humanoid genetically-engineered animals. The name of the series (and of the creatures themselves) comes from the H. G. Wells novel The Island of Dr. Moreau. In the Wells novel, humanoid animals were created surgically, though this detail has been changed to be genetic manipulation in most film adaptations.

The Neanderthal Parallax novel by Robert J. Sawyer depicts a eugenic society that has benefitted immensely from the sterilization of dangerous criminals as well as preventing the 5% least intelligent from procreating for ten generations.

In the Neon Genesis Evangelion anime series, the character Rei Ayanami is implied to be a lab-created being combining human and angelic DNA. (compare to the Biblical Nephilim)

Genetic engineering (or something very like it) features prominently in Last and First Men, a 1930 novel by Olaf Stapledon.

Genetic engineering is depicted as widespread in the civilized world of Oryx and Crake. Prior to the apocalypse, though, its use among humans is not mentioned. Author Margaret Atwood describes many transgenic creatures such as Pigoons (though originally designed to be harvested for organs, post-apocalyptic-plague, they become more intelligent and vicious, traveling in packs), Snats (snake-rat hybrids who may or may not be extinct), wolvogs (wolf-dog hybrids), and the relatively harmless “rakunks” (skunk-raccoon hybrids, originally designed as pets with no scent glands).

In Plague, a 1979 film, a bacterium in an agricultural experiment accidentally escapes from a research laboratory in Canada, reaching the American Northeast and Great Britain.

Using a method similar to the DNA Resequencer from Stargate SG-1, and even called DNA Resequencing, the Operation Overdrive Power Rangers were given powers of superhuman strength, enhanced hearing, enhanced eyesight, super bouncing, super speed, and invisibility.

Quake II and Quake 4, released in 1997 and 2005, contain genetically-engineered Stroggs.

In the long-running 2006 series Rogue Trooper, the eponymous hero is a Genetic Infantryman, one of an elite group of supersoldiers genetically modified to resist the poisons left in the Nu-Earth atmosphere by decades of war. The original concept from the pages of 80s cult sci-fi comic 2000 AD (of Judge Dredd fame).

James Blish’s The Seedling Stars (1956) is the classic story of controlled mutation for adaptability. In this novel (originally a series of short stories) the Adapted Men are reshaped human beings, designed for life on a variety of other planets. This is one of science fiction’s most unreservedly optimistic accounts to date of technological efforts to reshape human beings.

In “The Man Who Grew Too Much” episode (2014), Sideshow Bob steals DNA from a GMO company, thus making himself the very first genetically engineered human, and attempts to combine his DNA with that of the smartest people ever to exist on Earth.

In Sleeper, a 1973 parody of many science fiction tropes, genetically modified crops are shown to grow gigantic.

The short-lived 1990s television series Space: Above and Beyond includes a race of genetically engineered and artificially gestated humans who are born at the physical age of 18, and are collectively known as In Vitros or sometimes, derogatorily, “tanks” or “nipple-necks”. At the time of the series storyline, this artificial human race was integrated with the parent species, but significant discrimination still occurred.

The Ultimate Life Form project that produced Shadow the Hedgehog and Biolizard in the Sonic the Hedgehog series was a genetic engineering project.

In the Star Trek universe, genetic engineering has featured in a couple of films, and a number of television episodes.

The Breen, the Dominion, Species 8472, the Xindi, and the Federation use technology with organic components.

Khan Noonien Singh, who appeared in Space Seed and Star Trek II: The Wrath of Khan, was a product of genetic engineering. His physical structure was modified to make him stronger and to give him greater stamina than a regular human. His mind was also enhanced. However, the creation of Khan would have serious consequences because the superior abilities given to him created superior ambition. Along with other enhanced individuals, they tried to take over the planet. When they were reawakened by the Enterprise, Khan set himself to taking over the universe. Later, he became consumed by grief and rage, and set himself on the goal of destroying Kirk.

Others of these genetically enhanced augments wreaked havoc in the 22nd century, and eventually some of their enhanced DNA was blended with Klingon DNA, creating the human-looking Klingons of the early 23rd century (See Star Trek: Enterprise episodes “Affliction” and “Divergence”).

Because of the experiences with genetic engineering, the Federation had banned it except to correct genetic birth defects, but a number of parents still illegally subjected their children to genetic engineering for a variety of reasons. This often created brilliant but unstable individuals. Such children are not allowed to serve in Starfleet or practice medicine, though Julian Bashir is a notable exception to this. Despite the ban, the Federation allowed the Darwin station to conduct human genetic engineering, which resulted in a telepathic, telekentic humans with a very effective immune system.

In Attack of the Clones, the Kamino cloners who created the clone army for the Galactic Republic had used engineering to enhance their clones. They modified the genetic structure of all but one to accelerate their growth rate, make them less independent, and make them better suited to combat operations.

Later, the Yuuzhan Vong are a race who exclusively use organic technology and regard mechanical technology as heresy. Everything from starships to communications devices to weapons are bred and grown to suit their needs.

In the show Stargate SG-1, the DNA Resequencer was a device built by the Ancients, designed to make extreme upgrades to humans by realigning their DNA and upgrading their brain activity. The machine gave them superhuman abilities, such as telekensis, telepathy, precognition, superhuman senses, strength, and intellect, the power to heal at an incredible rate, and the power to heal others by touch.

In the futuristic tabletop and video game series, Warhammer 40,000, the Imperium of Man uses genetic engineering to enhance the abilities of various militant factions such as the Space Marines, the Thunder Warriors, and the Adeptus Custodes. In the case of Space Marines, a series of synthesized, metamorphosis-inducing organs, known as gene seed, is made from the genome of the twenty original Primarchs and used to start the transformation of these superhuman warriors.

At the same time, the Tau Empire uses a form of eugenic breeding to improve the physical and mental condition of its various castes.

In the e-book, Methuselah’s Virus, an ageing pharmaceutical billionaire accidentally creates a contagious virus capable of infecting people with extreme longevity when his genetic engineering experiment goes wrong. The novel then examines the problem of what happens if Methuselah’s Virus is at risk of spreading to everyone on the entire planet.

In World Hunger, author Brian Kenneth Swain paints the harrowing picture of a life sciences company that field tests a new strain of genetically modified crop, the unexpected side effect of which is the creation of several new species of large and very aggressive insects.

Genetic engineering is an essential theme of the illustrated book Man After Man: An Anthropology of the Future by Dougal Dixon, where it is used to colonize other star systems and save the humans of Earth from extinction.

The Survival Gene e-book contains the author Artsun Akopyan’s idea that people can’t preserve nature as it is forever, so they’ll have to change their own genetics in the future or die. In the novel, wave genetics is used to save humankind and all life on Earth.

A series of books by David Brin in which humans have encountered the Five Galazies, a multitude of sentient species which all practice Uplift raising species to sapience through genetic engineering. Humans, believing they have risen to sapience through evolution alone, are seen as heretics. But they have some status because at the time of contact humans had already Uplifted two species chimpanzees and bottlenose dolphins.

Eugenics is a recurrent theme in science fiction, often with both dystopian and utopian elements. The two giant contributions in this field are the novel Brave New World (1932) by Aldous Huxley, which describes a society where control of human biology by the state results in permanent social stratification.

There tends to be a eugenic undercurrent in the science fiction concept of the supersoldier. Several depictions of these supersoldiers usually have them bred for combat or genetically selected for attributes that are beneficial to modern or future combat.

The Brave New World theme also plays a role in the 1997 film Gattaca, whose plot turns around reprogenetics, genetic testing, and the social consequences of eugenics. Boris Vian (under the pseudonym Vernon Sullivan) takes a more light-hearted approach in his novel Et on tuera tous les affreux (“And we’ll kill all the ugly ones”).

Other novels touching upon the subject include The Gate to Women’s Country by Sheri S. Tepper and That Hideous Strength by C. S. Lewis. The Eugenics Wars are a significant part of the background story of the Star Trek universe (episodes “Space Seed”, “Borderland”, “Cold Station 12”, “The Augments” and the film Star Trek II: The Wrath of Khan). Eugenics also plays a significant role in the Neanderthal Parallax trilogy where eugenics-practicing Neanderthals from a near-utopian parallel world create a gateway to earth. Cowl by Neal Asher describes the collapse of western civilization due to dysgenics. Also Eugenics is the name for the medical company in La Foire aux immortels book by Enki Bilal and on the Immortel (Ad Vitam) movie by the same author.

In Frank Herbert’s Dune series of novels, selective breeding programs form a significant theme. Early in the series, the Bene Gesserit religious order manipulates breeding patterns over many generations in order to create the Kwisatz Haderach. In God Emperor of Dune, the emperor Leto II again manipulates human breeding in order to achieve his own ends. The Bene Tleilaxu also employed genetic engineering to create human beings with specific genetic attributes. The Dune series ended with causal determinism playing a large role in the development of behavior, but the eugenics theme remained a crucial part of the story.

In Orson Scott Card’s novel Ender’s Game, Ender is only allowed to be conceived because of a special government exception due to his parent’s high intelligence and the extraordinary performance of his siblings. In Ender’s Shadow, Bean is a test-tube baby and the result of a failed eugenics experiment aimed at creating child geniuses.

In the novels Methuselah’s Children and Time Enough for Love by Robert A. Heinlein, a large trust fund is created to give financial encouragement to marriage among people (the Howard Families) whose parents and grandparents were long lived. The result is a subset of Earth’s population who has significantly above-average life spans. Members of this group appear in many of the works by the same author.

In the 1982 Robert Heinlein novel Friday, the main character has been genetically engineered from multiple sets of donors, including, as she finds out later her boss. These enhancements give her superior strength, speed, eyesight in addition to healing and other advanced attributes. Creations like her are considered to be AP’s (Artificial Person).

In Eoin Colfer’s book The Supernaturalist, Ditto is a Bartoli Baby, which is the name for a failed experiment of the famed Dr. Bartoli. Bartoli tried to create a superior race of humans, but they ended in arrested development, with mutations including extrasensory perception and healing hands.

In Larry Niven’s Ringworld series, the character Teela Brown is a result of several generations of winners of the “Birthright Lottery”, a system which attempts to encourage lucky people to breed, treating good luck as a genetic trait.

In season 2 of Dark Angel, the main ‘bad guy’ Ames White is a member of a cult known as the Conclave which has infiltrated various levels of society to breed super-humans. They are trying to exterminate all the Transgenics, including the main character Max Guevara, whom they view as being genetically unclean for having some animal DNA spliced with human.

In the movie Immortel (Ad Vitam), Director/Writer Enki Bilal titled the name of the evil corrupt organization specializing in genetic manipulation, and some very disturbing genetic “enhancement” eugenics. Eugenics has come to be a powerful organization and uses people and mutants of “lesser” genetic stock as guinea pigs. The movie is based on the Nikopol trilogy in Heavy Metal comic books.

In the video game Grand Theft Auto: Vice City, a fictional character called Pastor Richards, a caricature of an extreme and insane televangelist, is featured as a guest on a discussion radio show about morality. On this show, he describes shooting people who do not agree with him and who are not “morally correct”, which the show’s host describes as “amateur eugenics”.

In the 2006 Mike Judge film Idiocracy, a fictional character, pvt. Joe Bauers, aka Not Sure (played by Luke Wilson), awakens from a cryogenic stasis in the year 2505 into a world devastated by dysgenic degeneration. Bauers, who was chosen for his averageness, is discovered to be the smartest human alive and eventually becomes president of the United States.

The manga series Battle Angel Alita and its sequel Battle Angel Alita: Last Order (Gunnm and Gunnm: Last Order as it is known in Japan) by Yukito Kishiro, contains multiple references to the theme of eugenics. The most obvious is the sky city Tiphares (Salem in Japanese edition). Dr. Desty Nova, in the first series in Volume 9, reveals the eugenical nature of the city to Alita (Gally or Yoko) and it is further explored in the sequel series. A James Cameron movie based on the series is due for release on 2018.[10]

In the French 2000 police drama Crimson Rivers, inspectors Pierre Niemans (played by Jean Reno) and his colleague Max Kerkerian (Vincent Cassel) attempt to solve series of murders triggered by eugenics experiment that was going on for years in university town of Guernon.

In the Cosmic Era universe of the Gundam anime series (Mobile Suit Gundam SEED), war is fought between the normal human beings without genetic enhancements, also known as the Naturals, and the Coordinators, who are genetically enhanced. It explores the pros and cons as well as possible repercussions from Eugenics

The Khommites of planet Khomm practice this through the method of self-cloning, believing they are perfect.

The book Uglies, part of a four-book series by Scott Westerfeld, revolves around a girl named Tally who lives in a world where everyone at the age of sixteen receives extensive cosmetic surgery to turn into “Pretties” and join society. Although it deals with extreme cosmetic surgery, the utopian (or dystopian, depending on one’s interpretation) ideals in the book are similar to those present in the books mentioned above.

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Genetic engineering in science fiction – Wikipedia

Human Genetic Engineering Effects

Some people can think of Human Genetic Engineering as a thing that makes them live a healthier life for a long time. People can think of it as a something straight from the heaven or a programmed human being. Genetic engineering is a concept that can be used for enhancing the life of human beings.

However, Human Genetic Engineering Effects are also there that can harm humans. A lot of doctors or scientists involved in gene engineering believe that if the research produces accurate and effective manipulation of DNA in the humans, then they can make medicines for diseases that have no cure. This will also enable the doctors to make changes in the genes of a child before the birth of that child, so there will be no defects on a child from birth.

This process can also be applied on curing hereditary disease. It will prevent the disease from carrying forward to other coming generations. This research primarily focused on being applied on families that have a history of suffering from diseases. It will fix the wrong positioning of the genes. TheHuman Genetic Engineering Effects are in its application towards animals and plants that have been modified genetically. When farmers make use of gene-engineering for breeding plants, then this will result in fast production of food items. Fast and increased production will also put down the prices of several food items. Human Genetic Engineering can also add taste and nutrition to different food items.

Human Genetic Engineering Effects can also help in fighting with severe uncured diseases. Those who suffer from life threatening diseases like cancer or AIDS can have a better idea about maintaining their lives according to the circumstances. This can only be done with the help of Human Genetic Engineering.

Hereditary diseases will not trouble any person, and nor there will be any fear of deadly virus taking place in people on all corners of the world. Human Genetic Engineering can achieve all these things in a theoretical way. Human Genetic Engineering Effects can also be seen in societies concerning health. It has tremendous benefits on health.

Human Genetic Engineering can help people in fighting with cystic fibrosis problems. It also helps to fight against diabetes, and many other specific diseases. Bubble boy is also a disease that can be treated successfully with the help Human Genetic Engineering. It is also termed as Severe Combined Immune efficiency.

Gene mutation is the only thing responsible for the characterization of this deadly disease. This mutation causes ADA deficiencies that later result in destroying the immune system cells. Human Genetic Engineering Effects include ecological problems that might be present in organisms developed or generated by Human Genetic Engineering. However, it can leave positive impacts on a lot of diseases.

One cannot predict the changes that can occur with the use of species that generates with the help of Human Genetic Engineering Effects. A newly generated species creates ecology imbalances due to Human Genetic Engineering Effects. This is a similar case with exotic or natural species.

Human Genetic Engineering Effects

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Human Genetic Engineering Effects

Genetic engineering in science fiction – Wikipedia

In literature and especially in science fiction, genetic engineering has been used as a theme or a plot device in many stories.[1][2]

In his 1924 essay Daedalus, or Science and the Future, J. B. S. Haldane predicted a day when biologists would invent new algae to feed the world and ectogenetic children would be created and modified using eugenic selection. Aldous Huxley developed these ideas in a satirical direction for his 1932 novel Brave New World, in which ectogenetic embryos were developed in selected environments to create children of an ‘Alpha’, ‘Beta’, or ‘Gamma’ type.[3]

The advent of large-scale genetic engineering has increased its presence in fiction.[4][5] Genetics research consortia, such as the Wellcome Trust Sanger Institute, have felt the need to distinguish genetic engineering fact from fiction in explaining their work to the public,[1] and have explored the role that genetic engineering has played in the public perception of programs, such as the Human Genome Project.[6]

Beyond the usual library catalog classifications,[7] the Wellcome Trust Sanger Institute[1] and the NHGRI[6] have compiled catalogs of literature in various media with genetics and genetic engineering as a theme or plot device. Such compilations are also available at fan sites.[8]

In the 2000 television series Andromeda, the Nietzscheans (Homo sapiens invictus in Latin) are a race of genetically engineered humans who religiously follow the works of Friedrich Nietzsche, social Darwinism and Dawkinite genetic competitiveness. They claim to be physically perfect and are distinguished by bone blades protruding outwards from the wrist area.

In the book 2312 by Kim Stanley Robinson, genetic engineering of humans, plants and animals and how that affects a society spread over the solar system is explored.

In the Animorphs book series, race of aliens known as the Hork-Bajir were engineered by a race known as the Arns. Another race, the Iskhoots, are another example of genetic engineering. The outer body, the Isk, was created by the Yoort, who also modify themselves to be symbotic to the Isk. Also, a being known as the Ellimist has made species such as the Pemalites by this method.

In the 1983 film Anna to the Infinite Power, the main character was one of seven genetically cloned humans created by Anna Zimmerman as a way to groom a perfect person in her image. After her death, her work was carried on by her successor Dr. Henry Jelliff, who had other plans for the project. But in the end we learn that her original genetic creation, Michaela Dupont, has already acquired her creator’s abilities, including how to build a genetic replicator from scratch.

The 1996 video game series Resident Evil involves the creation of genetically engineered viruses which turn humans and animals into organisms such as zombies, the Tyrants or Hunters by a worldwide pharmaceutical company called the Umbrella Corporation.

In the video game series BioShock, most of the enemies in both BioShock and BioShock 2, referred to as “splicers”, as well as the player, gain superpowers and enhance their physical and mental capabilities by means of genetically engineered plasmids, created by use of ADAM stem cells secreted by a species of sea slug.[9]

The novel Beggars in Spain by Nancy Kress and its sequels are widely recognized by science fiction critics as among the most sophisticated fictional treatments of genetic engineering. They portray genetically-engineered characters whose abilities are far greater than those of ordinary humans (e.g. they are effectively immortal and they function without needing to sleep). At issue is what responsibility they have to use their abilities to help “normal” human beings. Kress explores libertarian and more collectivist philosophies, attempting to define the extent of people’s mutual responsibility for each other’s welfare.

In the Battletech science fiction series, the Clans have developed a genetic engineering program for their warriors, consisting of eugenics and the use of artificial wombs.

In The Champion Maker, a novel by Kevin Joseph, a track coach and a teenage phenom stumble upon a dark conspiracy involving genetic engineering while pursuing Olympic gold.

In the CoDominium series, the planet Sauron develops a supersoldier program. The result were the Sauron Cyborgs, and soldiers. The Cyborgs, who made up only a very small part of the population of Sauron, were part highly genetically engineered human, and part machine. Cyborgs held very high status in Sauron society.

Sauron soldiers, who made up the balance of the population, were the result of generations of genetic engineering. The Sauron soldiers had a variety of physical characteristics and abilities that made the soldiers the best in combat and survival in many hostile environments. For instance, their bones were stronger than unmodified humans. Their lungs extract oxygen more efficiently than normal unmodified humans, allowing them to exert themselves without getting short of breath, or function at high altitudes. Sauron soldiers also have the ability to change the focal length of their eyes, so that they can “zoom” in on a distant object, much like an eagle.

The alien Moties also have used genetic engineering.

In the science fiction series Crest of the Stars, the Abh are a race of genetically engineered humans, who continue to practice the technology. All Abh have been adapted to live in zero-gravity environments, with the same features such as beauty, long life, lifelong youthful appearance, blue hair, and a “space sensory organ”.

In the 2000 TV series Dark Angel, the main character Max is one of a group of genetically engineered supersoldiers spliced with feline DNA.

In military science fiction 1993 television series Exosquad, the plot revolves around the conflict between Terrans (baseline humans) and Neosapiens, a race of genetically engineered sentient (and sterile) humanoids, who were originally bred for slave labour but revolted under the leadership of Phaeton and captured the Homeworlds (Earth, Venus and Mars). During the war, various sub-broods of Neosapiens were invented, such as, Neo Megas (intellectually superior to almost any being in the Solar System), Neo Warriors (cross-breeds with various animals) and Neo Lords (the ultimate supersoldiers).

Genetic modification is also found in the 2002 anime series Gundam SEED. It features enhanced humans called Coordinators who were created from ordinary humans through genetic modification.

In Marvel Comics, the 31st century adventurers called the Guardians of the Galaxy are genetically engineered residents of Mercury, Jupiter, and Pluto.

The 1997 film Gattaca deals with the idea of genetic engineering and eugenics as it projects what class relations would look like in a future society after a few generations of the possibility of genetic engineering.

In Marvel Comics, the Inhumans are the result of genetic engineering of early humans by the Kree alien race.

Rather than deliberate engineering, this 2017 novel by British author Steve Turnbull features a plague that carries genetic material across species, causing a wide variety of mutations. Human attempts to control this plague have resulted in a fascist dystopia.

In the Leviathan universe, a group known as the Darwinists use genetically engineered animals as weapons.

The 2000AD strip, Lobster Random features a former soldier-turned-torturer, who has been modified to not feel pain or need to sleep and has a pair of lobster claws grafted to his hips. This state has left him somewhat grouchy.

In Metal Gear Solid, the Genome Army were given gene therapy enhancements.

Also in the series, the Les Enfants Terribles project involved genetic engineering.

The Moreau series by S. Andrew Swann has as the central premise the proliferation of humanoid genetically-engineered animals. The name of the series (and of the creatures themselves) comes from the H. G. Wells novel The Island of Dr. Moreau. In the Wells novel, humanoid animals were created surgically, though this detail has been changed to be genetic manipulation in most film adaptations.

The Neanderthal Parallax novel by Robert J. Sawyer depicts a eugenic society that has benefitted immensely from the sterilization of dangerous criminals as well as preventing the 5% least intelligent from procreating for ten generations.

In the Neon Genesis Evangelion anime series, the character Rei Ayanami is implied to be a lab-created being combining human and angelic DNA. (compare to the Biblical Nephilim)

Genetic engineering (or something very like it) features prominently in Last and First Men, a 1930 novel by Olaf Stapledon.

Genetic engineering is depicted as widespread in the civilized world of Oryx and Crake. Prior to the apocalypse, though, its use among humans is not mentioned. Author Margaret Atwood describes many transgenic creatures such as Pigoons (though originally designed to be harvested for organs, post-apocalyptic-plague, they become more intelligent and vicious, traveling in packs), Snats (snake-rat hybrids who may or may not be extinct), wolvogs (wolf-dog hybrids), and the relatively harmless “rakunks” (skunk-raccoon hybrids, originally designed as pets with no scent glands).

In Plague, a 1978 film, a bacterium in an agricultural experiment accidentally escapes from a research laboratory in Canada, reaching the American Northeast and Great Britain.

Using a method similar to the DNA Resequencer from Stargate SG-1, and even called DNA Resequencing, the Operation Overdrive Power Rangers were given powers of superhuman strength, enhanced hearing, enhanced eyesight, super bouncing, super speed, and invisibility.

Quake II and Quake 4, released in 1997 and 2005, contain genetically-engineered Stroggs.

In the long-running 2006 series Rogue Trooper, the eponymous hero is a Genetic Infantryman, one of an elite group of supersoldiers genetically modified to resist the poisons left in the Nu-Earth atmosphere by decades of war. The original concept from the pages of 80s cult sci-fi comic 2000 AD (of Judge Dredd fame).

James Blish’s The Seedling Stars (1956) is the classic story of controlled mutation for adaptability. In this novel (originally a series of short stories) the Adapted Men are reshaped human beings, designed for life on a variety of other planets. This is one of science fiction’s most unreservedly optimistic accounts to date of technological efforts to reshape human beings.

In “The Man Who Grew Too Much” episode (2014), Sideshow Bob steals DNA from a GMO company, thus making himself the very first genetically engineered human, and attempts to combine his DNA with that of the smartest people ever to exist on Earth.

In Sleeper, a 1973 parody of many science fiction tropes, genetically modified crops are shown to grow gigantic.

The short-lived 1990s television series Space: Above and Beyond includes a race of genetically engineered and artificially gestated humans who are born at the physical age of 18, and are collectively known as In Vitros or sometimes, derogatorily, “tanks” or “nipple-necks”. At the time of the series storyline, this artificial human race was integrated with the parent species, but significant discrimination still occurred.

The Ultimate Life Form project that produced Shadow the Hedgehog and Biolizard in the Sonic the Hedgehog series was a genetic engineering project.

In the Star Trek universe, genetic engineering has featured in a couple of films, and a number of television episodes.

The Breen, the Dominion, Species 8472, the Xindi, and the Federation use technology with organic components.

Khan Noonien Singh, who appeared in Space Seed and Star Trek II: The Wrath of Khan, was a product of genetic engineering. His physical structure was modified to make him stronger and to give him greater stamina than a regular human. His mind was also enhanced. However, the creation of Khan would have serious consequences because the superior abilities given to him created superior ambition. Along with other enhanced individuals, they tried to take over the planet. When they were reawakened by the Enterprise, Khan set himself to taking over the universe. Later, he became consumed by grief and rage, and set himself on the goal of destroying Kirk.

Others of these genetically enhanced augments wreaked havoc in the 22nd century, and eventually some of their enhanced DNA was blended with Klingon DNA, creating the human-looking Klingons of the early 23rd century (See Star Trek: Enterprise episodes “Affliction” and “Divergence”).

Because of the experiences with genetic engineering, the Federation had banned it except to correct genetic birth defects, but a number of parents still illegally subjected their children to genetic engineering for a variety of reasons. This often created brilliant but unstable individuals. Such children are not allowed to serve in Starfleet or practice medicine, though Julian Bashir is a notable exception to this. Despite the ban, the Federation allowed the Darwin station to conduct human genetic engineering, which resulted in a telepathic, telekentic humans with a very effective immune system.

In Attack of the Clones, the Kamino cloners who created the clone army for the Galactic Republic had used engineering to enhance their clones. They modified the genetic structure of all but one to accelerate their growth rate, make them less independent, and make them better suited to combat operations.

Later, the Yuuzhan Vong are a race who exclusively use organic technology and regard mechanical technology as heresy. Everything from starships to communications devices to weapons are bred and grown to suit their needs.

In the show Stargate SG-1, the DNA Resequencer was a device built by the Ancients, designed to make extreme upgrades to humans by realigning their DNA and upgrading their brain activity. The machine gave them superhuman abilities, such as telekensis, telepathy, precognition, superhuman senses, strength, and intellect, the power to heal at an incredible rate, and the power to heal others by touch.

In the futuristic tabletop and video game series, Warhammer 40,000, the Imperium of Man uses genetic engineering to enhance the abilities of various militant factions such as the Space Marines, the Thunder Warriors, and the Adeptus Custodes. In the case of Space Marines, a series of synthesized, metamorphosis-inducing organs, known as gene seed, is made from the genome of the twenty original Primarchs and used to start the transformation of these superhuman warriors.

At the same time, the Tau Empire uses a form of eugenic breeding to improve the physical and mental condition of its various castes.

In the e-book, Methuselah’s Virus, an ageing pharmaceutical billionaire accidentally creates a contagious virus capable of infecting people with extreme longevity when his genetic engineering experiment goes wrong. The novel then examines the problem of what happens if Methuselah’s Virus is at risk of spreading to everyone on the entire planet.

In World Hunger, author Brian Kenneth Swain paints the harrowing picture of a life sciences company that field tests a new strain of genetically modified crop, the unexpected side effect of which is the creation of several new species of large and very aggressive insects.

Genetic engineering is an essential theme of the illustrated book Man After Man: An Anthropology of the Future by Dougal Dixon, where it is used to colonize other star systems and save the humans of Earth from extinction.

The Survival Gene e-book contains the author Artsun Akopyan’s idea that people can’t preserve nature as it is forever, so they’ll have to change their own genetics in the future or die. In the novel, wave genetics is used to save humankind and all life on Earth.

A series of books by David Brin in which humans have encountered the Five Galazies, a multitude of sentient species which all practice Uplift raising species to sapience through genetic engineering. Humans, believing they have risen to sapience through evolution alone, are seen as heretics. But they have some status because at the time of contact humans had already Uplifted two species chimpanzees and bottlenose dolphins.

Eugenics is a recurrent theme in science fiction, often with both dystopian and utopian elements. The two giant contributions in this field are the novel Brave New World (1932) by Aldous Huxley, which describes a society where control of human biology by the state results in permanent social stratification.

There tends to be a eugenic undercurrent in the science fiction concept of the supersoldier. Several depictions of these supersoldiers usually have them bred for combat or genetically selected for attributes that are beneficial to modern or future combat.

The Brave New World theme also plays a role in the 1997 film Gattaca, whose plot turns around reprogenetics, genetic testing, and the social consequences of eugenics. Boris Vian (under the pseudonym Vernon Sullivan) takes a more light-hearted approach in his novel Et on tuera tous les affreux (“And we’ll kill all the ugly ones”).

Other novels touching upon the subject include The Gate to Women’s Country by Sheri S. Tepper and That Hideous Strength by C. S. Lewis. The Eugenics Wars are a significant part of the background story of the Star Trek universe (episodes “Space Seed”, “Borderland”, “Cold Station 12”, “The Augments” and the film Star Trek II: The Wrath of Khan). Eugenics also plays a significant role in the Neanderthal Parallax trilogy where eugenics-practicing Neanderthals from a near-utopian parallel world create a gateway to earth. Cowl by Neal Asher describes the collapse of western civilization due to dysgenics. Also Eugenics is the name for the medical company in La Foire aux immortels book by Enki Bilal and on the Immortel (Ad Vitam) movie by the same author.

In Frank Herbert’s Dune series of novels, selective breeding programs form a significant theme. Early in the series, the Bene Gesserit religious order manipulates breeding patterns over many generations in order to create the Kwisatz Haderach. In God Emperor of Dune, the emperor Leto II again manipulates human breeding in order to achieve his own ends. The Bene Tleilaxu also employed genetic engineering to create human beings with specific genetic attributes. The Dune series ended with causal determinism playing a large role in the development of behavior, but the eugenics theme remained a crucial part of the story.

In Orson Scott Card’s novel Ender’s Game, Ender is only allowed to be conceived because of a special government exception due to his parent’s high intelligence and the extraordinary performance of his siblings. In Ender’s Shadow, Bean is a test-tube baby and the result of a failed eugenics experiment aimed at creating child geniuses.

In the novels Methuselah’s Children and Time Enough for Love by Robert A. Heinlein, a large trust fund is created to give financial encouragement to marriage among people (the Howard Families) whose parents and grandparents were long lived. The result is a subset of Earth’s population who has significantly above-average life spans. Members of this group appear in many of the works by the same author.

In the 1982 Robert Heinlein novel Friday, the main character has been genetically engineered from multiple sets of donors, including, as she finds out later her boss. These enhancements give her superior strength, speed, eyesight in addition to healing and other advanced attributes. Creations like her are considered to be AP’s (Artificial Person).

In Eoin Colfer’s book The Supernaturalist, Ditto is a Bartoli Baby, which is the name for a failed experiment of the famed Dr. Bartoli. Bartoli tried to create a superior race of humans, but they ended in arrested development, with mutations including extrasensory perception and healing hands.

In Larry Niven’s Ringworld series, the character Teela Brown is a result of several generations of winners of the “Birthright Lottery”, a system which attempts to encourage lucky people to breed, treating good luck as a genetic trait.

In season 2 of Dark Angel, the main ‘bad guy’ Ames White is a member of a cult known as the Conclave which has infiltrated various levels of society to breed super-humans. They are trying to exterminate all the Transgenics, including the main character Max Guevara, whom they view as being genetically unclean for having some animal DNA spliced with human.

In the movie Immortel (Ad Vitam), Director/Writer Enki Bilal titled the name of the evil corrupt organization specializing in genetic manipulation, and some very disturbing genetic “enhancement” eugenics. Eugenics has come to be a powerful organization and uses people and mutants of “lesser” genetic stock as guinea pigs. The movie is based on the Nikopol trilogy in Heavy Metal comic books.

In the video game Grand Theft Auto: Vice City, a fictional character called Pastor Richards, a caricature of an extreme and insane televangelist, is featured as a guest on a discussion radio show about morality. On this show, he describes shooting people who do not agree with him and who are not “morally correct”, which the show’s host describes as “amateur eugenics”.

In the 2006 Mike Judge film Idiocracy, a fictional character, pvt. Joe Bauers, aka Not Sure (played by Luke Wilson), awakens from a cryogenic stasis in the year 2505 into a world devastated by dysgenic degeneration. Bauers, who was chosen for his averageness, is discovered to be the smartest human alive and eventually becomes president of the United States.

The manga series Battle Angel Alita and its sequel Battle Angel Alita: Last Order (Gunnm and Gunnm: Last Order as it is known in Japan) by Yukito Kishiro, contains multiple references to the theme of eugenics. The most obvious is the sky city Tiphares (Salem in Japanese edition). Dr. Desty Nova, in the first series in Volume 9, reveals the eugenical nature of the city to Alita (Gally or Yoko) and it is further explored in the sequel series. A James Cameron movie based on the series is due for release on 2018.[10]

In the French 2000 police drama Crimson Rivers, inspectors Pierre Niemans (played by Jean Reno) and his colleague Max Kerkerian (Vincent Cassel) attempt to solve series of murders triggered by eugenics experiment that was going on for years in university town of Guernon.

In the Cosmic Era universe of the Gundam anime series (Mobile Suit Gundam SEED), war is fought between the normal human beings without genetic enhancements, also known as the Naturals, and the Coordinators, who are genetically enhanced. It explores the pros and cons as well as possible repercussions from Eugenics

The Khommites of planet Khomm practice this through the method of self-cloning, believing they are perfect.

The book Uglies, part of a four-book series by Scott Westerfeld, revolves around a girl named Tally who lives in a world where everyone at the age of sixteen receives extensive cosmetic surgery to turn into “Pretties” and join society. Although it deals with extreme cosmetic surgery, the utopian (or dystopian, depending on one’s interpretation) ideals in the book are similar to those present in the books mentioned above.

See the article here:

Genetic engineering in science fiction – Wikipedia

Gene therapy – Wikipedia

In the medicine field, gene therapy (also called human gene transfer) is the therapeutic delivery of nucleic acid into a patient’s cells as a drug to treat disease.[1][2] The first attempt at modifying human DNA was performed in 1980 by Martin Cline, but the first successful nuclear gene transfer in humans, approved by the National Institutes of Health, was performed in May 1989.[3] The first therapeutic use of gene transfer as well as the first direct insertion of human DNA into the nuclear genome was performed by French Anderson in a trial starting in September 1990.

Between 1989 and February 2016, over 2,300 clinical trials had been conducted, more than half of them in phase I.[4]

Not all medical procedures that introduce alterations to a patient’s genetic makeup can be considered gene therapy. Bone marrow transplantation and organ transplants in general have been found to introduce foreign DNA into patients.[5] Gene therapy is defined by the precision of the procedure and the intention of direct therapeutic effects.

Gene therapy was conceptualized in 1972, by authors who urged caution before commencing human gene therapy studies.

The first attempt, an unsuccessful one, at gene therapy (as well as the first case of medical transfer of foreign genes into humans not counting organ transplantation) was performed by Martin Cline on 10 July 1980.[6][7] Cline claimed that one of the genes in his patients was active six months later, though he never published this data or had it verified[8] and even if he is correct, it’s unlikely it produced any significant beneficial effects treating beta-thalassemia.

After extensive research on animals throughout the 1980s and a 1989 bacterial gene tagging trial on humans, the first gene therapy widely accepted as a success was demonstrated in a trial that started on 14 September 1990, when Ashi DeSilva was treated for ADA-SCID.[9]

The first somatic treatment that produced a permanent genetic change was performed in 1993.[citation needed]

Gene therapy is a way to fix a genetic problem at its source. The polymers are either translated into proteins, interfere with target gene expression, or possibly correct genetic mutations.

The most common form uses DNA that encodes a functional, therapeutic gene to replace a mutated gene. The polymer molecule is packaged within a “vector”, which carries the molecule inside cells.

Early clinical failures led to dismissals of gene therapy. Clinical successes since 2006 regained researchers’ attention, although as of 2014, it was still largely an experimental technique.[10] These include treatment of retinal diseases Leber’s congenital amaurosis[11][12][13][14] and choroideremia,[15] X-linked SCID,[16] ADA-SCID,[17][18] adrenoleukodystrophy,[19] chronic lymphocytic leukemia (CLL),[20] acute lymphocytic leukemia (ALL),[21] multiple myeloma,[22] haemophilia,[18] and Parkinson’s disease.[23] Between 2013 and April 2014, US companies invested over $600 million in the field.[24]

The first commercial gene therapy, Gendicine, was approved in China in 2003 for the treatment of certain cancers.[25] In 2011 Neovasculgen was registered in Russia as the first-in-class gene-therapy drug for treatment of peripheral artery disease, including critical limb ischemia.[26] In 2012 Glybera, a treatment for a rare inherited disorder, became the first treatment to be approved for clinical use in either Europe or the United States after its endorsement by the European Commission.[10][27]

Following early advances in genetic engineering of bacteria, cells, and small animals, scientists started considering how to apply it to medicine. Two main approaches were considered replacing or disrupting defective genes.[28] Scientists focused on diseases caused by single-gene defects, such as cystic fibrosis, haemophilia, muscular dystrophy, thalassemia, and sickle cell anemia. Glybera treats one such disease, caused by a defect in lipoprotein lipase.[27]

DNA must be administered, reach the damaged cells, enter the cell and either express or disrupt a protein.[29] Multiple delivery techniques have been explored. The initial approach incorporated DNA into an engineered virus to deliver the DNA into a chromosome.[30][31] Naked DNA approaches have also been explored, especially in the context of vaccine development.[32]

Generally, efforts focused on administering a gene that causes a needed protein to be expressed. More recently, increased understanding of nuclease function has led to more direct DNA editing, using techniques such as zinc finger nucleases and CRISPR. The vector incorporates genes into chromosomes. The expressed nucleases then knock out and replace genes in the chromosome. As of 2014 these approaches involve removing cells from patients, editing a chromosome and returning the transformed cells to patients.[33]

Gene editing is a potential approach to alter the human genome to treat genetic diseases,[34] viral diseases,[35] and cancer.[36] As of 2016 these approaches were still years from being medicine.[37][38]

Gene therapy may be classified into two types:

In somatic cell gene therapy (SCGT), the therapeutic genes are transferred into any cell other than a gamete, germ cell, gametocyte, or undifferentiated stem cell. Any such modifications affect the individual patient only, and are not inherited by offspring. Somatic gene therapy represents mainstream basic and clinical research, in which therapeutic DNA (either integrated in the genome or as an external episome or plasmid) is used to treat disease.

Over 600 clinical trials utilizing SCGT are underway in the US. Most focus on severe genetic disorders, including immunodeficiencies, haemophilia, thalassaemia, and cystic fibrosis. Such single gene disorders are good candidates for somatic cell therapy. The complete correction of a genetic disorder or the replacement of multiple genes is not yet possible. Only a few of the trials are in the advanced stages.[39]

In germline gene therapy (GGT), germ cells (sperm or egg cells) are modified by the introduction of functional genes into their genomes. Modifying a germ cell causes all the organism’s cells to contain the modified gene. The change is therefore heritable and passed on to later generations. Australia, Canada, Germany, Israel, Switzerland, and the Netherlands[40] prohibit GGT for application in human beings, for technical and ethical reasons, including insufficient knowledge about possible risks to future generations[40] and higher risks versus SCGT.[41] The US has no federal controls specifically addressing human genetic modification (beyond FDA regulations for therapies in general).[40][42][43][44]

The delivery of DNA into cells can be accomplished by multiple methods. The two major classes are recombinant viruses (sometimes called biological nanoparticles or viral vectors) and naked DNA or DNA complexes (non-viral methods).

In order to replicate, viruses introduce their genetic material into the host cell, tricking the host’s cellular machinery into using it as blueprints for viral proteins. Retroviruses go a stage further by having their genetic material copied into the genome of the host cell. Scientists exploit this by substituting a virus’s genetic material with therapeutic DNA. (The term ‘DNA’ may be an oversimplification, as some viruses contain RNA, and gene therapy could take this form as well.) A number of viruses have been used for human gene therapy, including retroviruses, adenoviruses, herpes simplex, vaccinia, and adeno-associated virus.[4] Like the genetic material (DNA or RNA) in viruses, therapeutic DNA can be designed to simply serve as a temporary blueprint that is degraded naturally or (at least theoretically) to enter the host’s genome, becoming a permanent part of the host’s DNA in infected cells.

Non-viral methods present certain advantages over viral methods, such as large scale production and low host immunogenicity. However, non-viral methods initially produced lower levels of transfection and gene expression, and thus lower therapeutic efficacy. Later technology remedied this deficiency.[citation needed]

Methods for non-viral gene therapy include the injection of naked DNA, electroporation, the gene gun, sonoporation, magnetofection, the use of oligonucleotides, lipoplexes, dendrimers, and inorganic nanoparticles.

Some of the unsolved problems include:

Three patients’ deaths have been reported in gene therapy trials, putting the field under close scrutiny. The first was that of Jesse Gelsinger in 1999. Jesse Gelsinger died because of immune rejection response.[51] One X-SCID patient died of leukemia in 2003.[9] In 2007, a rheumatoid arthritis patient died from an infection; the subsequent investigation concluded that the death was not related to gene therapy.[52]

In 1972 Friedmann and Roblin authored a paper in Science titled “Gene therapy for human genetic disease?”[53] Rogers (1970) was cited for proposing that exogenous good DNA be used to replace the defective DNA in those who suffer from genetic defects.[54]

In 1984 a retrovirus vector system was designed that could efficiently insert foreign genes into mammalian chromosomes.[55]

The first approved gene therapy clinical research in the US took place on 14 September 1990, at the National Institutes of Health (NIH), under the direction of William French Anderson.[56] Four-year-old Ashanti DeSilva received treatment for a genetic defect that left her with ADA-SCID, a severe immune system deficiency. The defective gene of the patient’s blood cells was replaced by the functional variant. Ashantis immune system was partially restored by the therapy. Production of the missing enzyme was temporarily stimulated, but the new cells with functional genes were not generated. She led a normal life only with the regular injections performed every two months. The effects were successful, but temporary.[57]

Cancer gene therapy was introduced in 1992/93 (Trojan et al. 1993).[58] The treatment of glioblastoma multiforme, the malignant brain tumor whose outcome is always fatal, was done using a vector expressing antisense IGF-I RNA (clinical trial approved by NIH protocolno.1602 November 24, 1993,[59] and by the FDA in 1994). This therapy also represents the beginning of cancer immunogene therapy, a treatment which proves to be effective due to the anti-tumor mechanism of IGF-I antisense, which is related to strong immune and apoptotic phenomena.

In 1992 Claudio Bordignon, working at the Vita-Salute San Raffaele University, performed the first gene therapy procedure using hematopoietic stem cells as vectors to deliver genes intended to correct hereditary diseases.[60] In 2002 this work led to the publication of the first successful gene therapy treatment for adenosine deaminase deficiency (ADA-SCID). The success of a multi-center trial for treating children with SCID (severe combined immune deficiency or “bubble boy” disease) from 2000 and 2002, was questioned when two of the ten children treated at the trial’s Paris center developed a leukemia-like condition. Clinical trials were halted temporarily in 2002, but resumed after regulatory review of the protocol in the US, the United Kingdom, France, Italy, and Germany.[61]

In 1993 Andrew Gobea was born with SCID following prenatal genetic screening. Blood was removed from his mother’s placenta and umbilical cord immediately after birth, to acquire stem cells. The allele that codes for adenosine deaminase (ADA) was obtained and inserted into a retrovirus. Retroviruses and stem cells were mixed, after which the viruses inserted the gene into the stem cell chromosomes. Stem cells containing the working ADA gene were injected into Andrew’s blood. Injections of the ADA enzyme were also given weekly. For four years T cells (white blood cells), produced by stem cells, made ADA enzymes using the ADA gene. After four years more treatment was needed.[62]

Jesse Gelsinger’s death in 1999 impeded gene therapy research in the US.[63][64] As a result, the FDA suspended several clinical trials pending the reevaluation of ethical and procedural practices.[65]

The modified cancer gene therapy strategy of antisense IGF-I RNA (NIH n 1602)[59] using antisense / triple helix anti-IGF-I approach was registered in 2002 by Wiley gene therapy clinical trial – n 635 and 636. The approach has shown promising results in the treatment of six different malignant tumors: glioblastoma, cancers of liver, colon, prostate, uterus, and ovary (Collaborative NATO Science Programme on Gene Therapy USA, France, Poland n LST 980517 conducted by J. Trojan) (Trojan et al., 2012). This anti-gene antisense/triple helix therapy has proven to be efficient, due to the mechanism stopping simultaneously IGF-I expression on translation and transcription levels, strengthening anti-tumor immune and apoptotic phenomena.

Sickle-cell disease can be treated in mice.[66] The mice which have essentially the same defect that causes human cases used a viral vector to induce production of fetal hemoglobin (HbF), which normally ceases to be produced shortly after birth. In humans, the use of hydroxyurea to stimulate the production of HbF temporarily alleviates sickle cell symptoms. The researchers demonstrated this treatment to be a more permanent means to increase therapeutic HbF production.[67]

A new gene therapy approach repaired errors in messenger RNA derived from defective genes. This technique has the potential to treat thalassaemia, cystic fibrosis and some cancers.[68]

Researchers created liposomes 25 nanometers across that can carry therapeutic DNA through pores in the nuclear membrane.[69]

In 2003 a research team inserted genes into the brain for the first time. They used liposomes coated in a polymer called polyethylene glycol, which unlike viral vectors, are small enough to cross the bloodbrain barrier.[70]

Short pieces of double-stranded RNA (short, interfering RNAs or siRNAs) are used by cells to degrade RNA of a particular sequence. If a siRNA is designed to match the RNA copied from a faulty gene, then the abnormal protein product of that gene will not be produced.[71]

Gendicine is a cancer gene therapy that delivers the tumor suppressor gene p53 using an engineered adenovirus. In 2003, it was approved in China for the treatment of head and neck squamous cell carcinoma.[25]

In March researchers announced the successful use of gene therapy to treat two adult patients for X-linked chronic granulomatous disease, a disease which affects myeloid cells and damages the immune system. The study is the first to show that gene therapy can treat the myeloid system.[72]

In May a team reported a way to prevent the immune system from rejecting a newly delivered gene.[73] Similar to organ transplantation, gene therapy has been plagued by this problem. The immune system normally recognizes the new gene as foreign and rejects the cells carrying it. The research utilized a newly uncovered network of genes regulated by molecules known as microRNAs. This natural function selectively obscured their therapeutic gene in immune system cells and protected it from discovery. Mice infected with the gene containing an immune-cell microRNA target sequence did not reject the gene.

In August scientists successfully treated metastatic melanoma in two patients using killer T cells genetically retargeted to attack the cancer cells.[74]

In November researchers reported on the use of VRX496, a gene-based immunotherapy for the treatment of HIV that uses a lentiviral vector to deliver an antisense gene against the HIV envelope. In a phase I clinical trial, five subjects with chronic HIV infection who had failed to respond to at least two antiretroviral regimens were treated. A single intravenous infusion of autologous CD4 T cells genetically modified with VRX496 was well tolerated. All patients had stable or decreased viral load; four of the five patients had stable or increased CD4 T cell counts. All five patients had stable or increased immune response to HIV antigens and other pathogens. This was the first evaluation of a lentiviral vector administered in a US human clinical trial.[75][76]

In May researchers announced the first gene therapy trial for inherited retinal disease. The first operation was carried out on a 23-year-old British male, Robert Johnson, in early 2007.[77]

Leber’s congenital amaurosis is an inherited blinding disease caused by mutations in the RPE65 gene. The results of a small clinical trial in children were published in April.[11] Delivery of recombinant adeno-associated virus (AAV) carrying RPE65 yielded positive results. In May two more groups reported positive results in independent clinical trials using gene therapy to treat the condition. In all three clinical trials, patients recovered functional vision without apparent side-effects.[11][12][13][14]

In September researchers were able to give trichromatic vision to squirrel monkeys.[78] In November 2009, researchers halted a fatal genetic disorder called adrenoleukodystrophy in two children using a lentivirus vector to deliver a functioning version of ABCD1, the gene that is mutated in the disorder.[79]

An April paper reported that gene therapy addressed achromatopsia (color blindness) in dogs by targeting cone photoreceptors. Cone function and day vision were restored for at least 33 months in two young specimens. The therapy was less efficient for older dogs.[80]

In September it was announced that an 18-year-old male patient in France with beta-thalassemia major had been successfully treated.[81] Beta-thalassemia major is an inherited blood disease in which beta haemoglobin is missing and patients are dependent on regular lifelong blood transfusions.[82] The technique used a lentiviral vector to transduce the human -globin gene into purified blood and marrow cells obtained from the patient in June 2007.[83] The patient’s haemoglobin levels were stable at 9 to 10 g/dL. About a third of the hemoglobin contained the form introduced by the viral vector and blood transfusions were not needed.[83][84] Further clinical trials were planned.[85] Bone marrow transplants are the only cure for thalassemia, but 75% of patients do not find a matching donor.[84]

Cancer immunogene therapy using modified antigene, antisense/triple helix approach was introduced in South America in 2010/11 in La Sabana University, Bogota (Ethical Committee 14 December 2010, no P-004-10). Considering the ethical aspect of gene diagnostic and gene therapy targeting IGF-I, the IGF-I expressing tumors i.e. lung and epidermis cancers were treated (Trojan et al. 2016).[86][87]

In 2007 and 2008, a man (Timothy Ray Brown) was cured of HIV by repeated hematopoietic stem cell transplantation (see also allogeneic stem cell transplantation, allogeneic bone marrow transplantation, allotransplantation) with double-delta-32 mutation which disables the CCR5 receptor. This cure was accepted by the medical community in 2011.[88] It required complete ablation of existing bone marrow, which is very debilitating.

In August two of three subjects of a pilot study were confirmed to have been cured from chronic lymphocytic leukemia (CLL). The therapy used genetically modified T cells to attack cells that expressed the CD19 protein to fight the disease.[20] In 2013, the researchers announced that 26 of 59 patients had achieved complete remission and the original patient had remained tumor-free.[89]

Human HGF plasmid DNA therapy of cardiomyocytes is being examined as a potential treatment for coronary artery disease as well as treatment for the damage that occurs to the heart after myocardial infarction.[90][91]

In 2011 Neovasculgen was registered in Russia as the first-in-class gene-therapy drug for treatment of peripheral artery disease, including critical limb ischemia; it delivers the gene encoding for VEGF.[92][26] Neovasculogen is a plasmid encoding the CMV promoter and the 165 amino acid form of VEGF.[93][94]

The FDA approved Phase 1 clinical trials on thalassemia major patients in the US for 10 participants in July.[95] The study was expected to continue until 2015.[85]

In July 2012, the European Medicines Agency recommended approval of a gene therapy treatment for the first time in either Europe or the United States. The treatment used Alipogene tiparvovec (Glybera) to compensate for lipoprotein lipase deficiency, which can cause severe pancreatitis.[96] The recommendation was endorsed by the European Commission in November 2012[10][27][97][98] and commercial rollout began in late 2014.[99] Alipogene tiparvovec was expected to cost around $1.6 million per treatment in 2012,[100] revised to $1 million in 2015,[101] making it the most expensive medicine in the world at the time.[102] As of 2016, only one person had been treated with drug.[103]

In December 2012, it was reported that 10 of 13 patients with multiple myeloma were in remission “or very close to it” three months after being injected with a treatment involving genetically engineered T cells to target proteins NY-ESO-1 and LAGE-1, which exist only on cancerous myeloma cells.[22]

In March researchers reported that three of five adult subjects who had acute lymphocytic leukemia (ALL) had been in remission for five months to two years after being treated with genetically modified T cells which attacked cells with CD19 genes on their surface, i.e. all B-cells, cancerous or not. The researchers believed that the patients’ immune systems would make normal T-cells and B-cells after a couple of months. They were also given bone marrow. One patient relapsed and died and one died of a blood clot unrelated to the disease.[21]

Following encouraging Phase 1 trials, in April, researchers announced they were starting Phase 2 clinical trials (called CUPID2 and SERCA-LVAD) on 250 patients[104] at several hospitals to combat heart disease. The therapy was designed to increase the levels of SERCA2, a protein in heart muscles, improving muscle function.[105] The FDA granted this a Breakthrough Therapy Designation to accelerate the trial and approval process.[106] In 2016 it was reported that no improvement was found from the CUPID 2 trial.[107]

In July researchers reported promising results for six children with two severe hereditary diseases had been treated with a partially deactivated lentivirus to replace a faulty gene and after 732 months. Three of the children had metachromatic leukodystrophy, which causes children to lose cognitive and motor skills.[108] The other children had Wiskott-Aldrich syndrome, which leaves them to open to infection, autoimmune diseases, and cancer.[109] Follow up trials with gene therapy on another six children with Wiskott-Aldrich syndrome were also reported as promising.[110][111]

In October researchers reported that two children born with adenosine deaminase severe combined immunodeficiency disease (ADA-SCID) had been treated with genetically engineered stem cells 18 months previously and that their immune systems were showing signs of full recovery. Another three children were making progress.[18] In 2014 a further 18 children with ADA-SCID were cured by gene therapy.[112] ADA-SCID children have no functioning immune system and are sometimes known as “bubble children.”[18]

Also in October researchers reported that they had treated six hemophilia sufferers in early 2011 using an adeno-associated virus. Over two years later all six were producing clotting factor.[18][113]

In January researchers reported that six choroideremia patients had been treated with adeno-associated virus with a copy of REP1. Over a six-month to two-year period all had improved their sight.[114][115] By 2016, 32 patients had been treated with positive results and researchers were hopeful the treatment would be long-lasting.[15] Choroideremia is an inherited genetic eye disease with no approved treatment, leading to loss of sight.

In March researchers reported that 12 HIV patients had been treated since 2009 in a trial with a genetically engineered virus with a rare mutation (CCR5 deficiency) known to protect against HIV with promising results.[116][117]

Clinical trials of gene therapy for sickle cell disease were started in 2014.[118][119] There is a need for high quality randomised controlled trials assessing the risks and benefits involved with gene therapy for people with sickle cell disease.[120]

In February LentiGlobin BB305, a gene therapy treatment undergoing clinical trials for treatment of beta thalassemia gained FDA “breakthrough” status after several patients were able to forgo the frequent blood transfusions usually required to treat the disease.[121]

In March researchers delivered a recombinant gene encoding a broadly neutralizing antibody into monkeys infected with simian HIV; the monkeys’ cells produced the antibody, which cleared them of HIV. The technique is named immunoprophylaxis by gene transfer (IGT). Animal tests for antibodies to ebola, malaria, influenza, and hepatitis were underway.[122][123]

In March, scientists, including an inventor of CRISPR, Jennifer Doudna, urged a worldwide moratorium on germline gene therapy, writing “scientists should avoid even attempting, in lax jurisdictions, germline genome modification for clinical application in humans” until the full implications “are discussed among scientific and governmental organizations”.[124][125][126][127]

In October, researchers announced that they had treated a baby girl, Layla Richards, with an experimental treatment using donor T-cells genetically engineered using TALEN to attack cancer cells. One year after the treatment she was still free of her cancer (a highly aggressive form of acute lymphoblastic leukaemia [ALL]).[128] Children with highly aggressive ALL normally have a very poor prognosis and Layla’s disease had been regarded as terminal before the treatment.[129]

In December, scientists of major world academies called for a moratorium on inheritable human genome edits, including those related to CRISPR-Cas9 technologies[130] but that basic research including embryo gene editing should continue.[131]

In April the Committee for Medicinal Products for Human Use of the European Medicines Agency endorsed a gene therapy treatment called Strimvelis[132][133] and the European Commission approved it in June.[134] This treats children born with adenosine deaminase deficiency and who have no functioning immune system. This was the second gene therapy treatment to be approved in Europe.[135]

In October, Chinese scientists reported they had started a trial to genetically modify T-cells from 10 adult patients with lung cancer and reinject the modified T-cells back into their bodies to attack the cancer cells. The T-cells had the PD-1 protein (which stops or slows the immune response) removed using CRISPR-Cas9.[136][137]

A 2016 Cochrane systematic review looking at data from four trials on topical cystic fibrosis transmembrane conductance regulator (CFTR) gene therapy does not support its clinical use as a mist inhaled into the lungs to treat cystic fibrosis patients with lung infections. One of the four trials did find weak evidence that liposome-based CFTR gene transfer therapy may lead to a small respiratory improvement for people with CF. This weak evidence is not enough to make a clinical recommendation for routine CFTR gene therapy.[138]

In February Kite Pharma announced results from a clinical trial of CAR-T cells in around a hundred people with advanced Non-Hodgkin lymphoma.[139]

In March, French scientists reported on clinical research of gene therapy to treat sickle-cell disease.[140]

In August, the FDA approved tisagenlecleucel for acute lymphoblastic leukemia.[141] Tisagenlecleucel is an adoptive cell transfer therapy for B-cell acute lymphoblastic leukemia; T cells from a person with cancer are removed, genetically engineered to make a specific T-cell receptor (a chimeric T cell receptor, or “CAR-T”) that reacts to the cancer, and are administered back to the person. The T cells are engineered to target a protein called CD19 that is common on B cells. This is the first form of gene therapy to be approved in the United States. In October, a similar therapy called axicabtagene ciloleucel was approved for non-Hodgkin lymphoma.[142]

In December the results of using an adeno-associated virus with blood clotting factor VIII to treat nine haemophilia A patients were published. Six of the seven patients on the high dose regime increased the level of the blood clotting VIII to normal levels. The low and medium dose regimes had no effect on the patient’s blood clotting levels.[143][144]

In December, the FDA approved Luxturna, the first in vivo gene therapy, for the treatment of blindness due to Leber’s congenital amaurosis.[145] The price of this treatment was 850,000 US dollars for both eyes.[146][147] CRISPR gene editing technology has also been used on mice to treat deafness due to the DFNA36 mutation, which also affects humans.[148]

Speculated uses for gene therapy include:

Gene Therapy techniques have the potential to provide alternative treatments for those with infertility. Recently, successful experimentation on mice has proven that fertility can be restored by using the gene therapy method, CRISPR.[149] Spermatogenical stem cells from another organism were transplanted into the testes of an infertile male mouse. The stem cells re-established spermatogenesis and fertility.[150]

Athletes might adopt gene therapy technologies to improve their performance.[151] Gene doping is not known to occur, but multiple gene therapies may have such effects. Kayser et al. argue that gene doping could level the playing field if all athletes receive equal access. Critics claim that any therapeutic intervention for non-therapeutic/enhancement purposes compromises the ethical foundations of medicine and sports.[152]

Genetic engineering could be used to cure diseases, but also to change physical appearance, metabolism, and even improve physical capabilities and mental faculties such as memory and intelligence. Ethical claims about germline engineering include beliefs that every fetus has a right to remain genetically unmodified, that parents hold the right to genetically modify their offspring, and that every child has the right to be born free of preventable diseases.[153][154][155] For parents, genetic engineering could be seen as another child enhancement technique to add to diet, exercise, education, training, cosmetics, and plastic surgery.[156][157] Another theorist claims that moral concerns limit but do not prohibit germline engineering.[158]

Possible regulatory schemes include a complete ban, provision to everyone, or professional self-regulation. The American Medical Associations Council on Ethical and Judicial Affairs stated that “genetic interventions to enhance traits should be considered permissible only in severely restricted situations: (1) clear and meaningful benefits to the fetus or child; (2) no trade-off with other characteristics or traits; and (3) equal access to the genetic technology, irrespective of income or other socioeconomic characteristics.”[159]

As early in the history of biotechnology as 1990, there have been scientists opposed to attempts to modify the human germline using these new tools,[160] and such concerns have continued as technology progressed.[161][162] With the advent of new techniques like CRISPR, in March 2015 a group of scientists urged a worldwide moratorium on clinical use of gene editing technologies to edit the human genome in a way that can be inherited.[124][125][126][127] In April 2015, researchers sparked controversy when they reported results of basic research to edit the DNA of non-viable human embryos using CRISPR.[149][163] A committee of the American National Academy of Sciences and National Academy of Medicine gave qualified support to human genome editing in 2017[164][165] once answers have been found to safety and efficiency problems “but only for serious conditions under stringent oversight.”[166]

Regulations covering genetic modification are part of general guidelines about human-involved biomedical research. There are no international treaties which are legally binding in this area, but there are recommendations for national laws from various bodies.

The Helsinki Declaration (Ethical Principles for Medical Research Involving Human Subjects) was amended by the World Medical Association’s General Assembly in 2008. This document provides principles physicians and researchers must consider when involving humans as research subjects. The Statement on Gene Therapy Research initiated by the Human Genome Organization (HUGO) in 2001 provides a legal baseline for all countries. HUGOs document emphasizes human freedom and adherence to human rights, and offers recommendations for somatic gene therapy, including the importance of recognizing public concerns about such research.[167]

No federal legislation lays out protocols or restrictions about human genetic engineering. This subject is governed by overlapping regulations from local and federal agencies, including the Department of Health and Human Services, the FDA and NIH’s Recombinant DNA Advisory Committee. Researchers seeking federal funds for an investigational new drug application, (commonly the case for somatic human genetic engineering,) must obey international and federal guidelines for the protection of human subjects.[168]

NIH serves as the main gene therapy regulator for federally funded research. Privately funded research is advised to follow these regulations. NIH provides funding for research that develops or enhances genetic engineering techniques and to evaluate the ethics and quality in current research. The NIH maintains a mandatory registry of human genetic engineering research protocols that includes all federally funded projects.

An NIH advisory committee published a set of guidelines on gene manipulation.[169] The guidelines discuss lab safety as well as human test subjects and various experimental types that involve genetic changes. Several sections specifically pertain to human genetic engineering, including Section III-C-1. This section describes required review processes and other aspects when seeking approval to begin clinical research involving genetic transfer into a human patient.[170] The protocol for a gene therapy clinical trial must be approved by the NIH’s Recombinant DNA Advisory Committee prior to any clinical trial beginning; this is different from any other kind of clinical trial.[169]

As with other kinds of drugs, the FDA regulates the quality and safety of gene therapy products and supervises how these products are used clinically. Therapeutic alteration of the human genome falls under the same regulatory requirements as any other medical treatment. Research involving human subjects, such as clinical trials, must be reviewed and approved by the FDA and an Institutional Review Board.[171][172]

Gene therapy is the basis for the plotline of the film I Am Legend[173] and the TV show Will Gene Therapy Change the Human Race?.[174] In 1994, gene therapy was a plot element in The Erlenmeyer Flask, The X-Files’ first season finale. It is also used in Stargate as a means of allowing humans to use Ancient technology.[175]

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Gene therapy – Wikipedia

Ethical Implications of Human Genetic Engineering | SAGE

DNA editing techniques have been available for decades and are crucial tools for understanding gene functions and molecular pathways. Recently, genome editing has stepped back into the limelight because of newer technologies that can quickly and efficiently modify genomes by introducing or genetically correcting mutations in human cells and animal models. These tools include Zinc Finger Nucleases (ZFNs), Transcription activator-like effector nucleases (TALENs), and the most recent player to join the ranks, Clustered Regularly Interspaced Short Palindromic repeats (CRISPR) (here, here). In a short time span, CRISPR/Cas9 has completely revolutionized the understanding of protein function, disease modeling, and potential therapeutic applications.

BACKGROUND on CRISPR/Cas9

The CRISPR/Cas9 system functions similarly to ZFNs and TALENs, it also takes advantage of a cells DNA repair machinery to delete (knock-out) or add in (knock-in) sequences of DNA. However, CRISPR/Cas9 offers several advantages: it is easier to target a specific gene of interest since designing the required CRISPR component is simple and efficient, whereas generating ZFNs and TALENs is more time consuming; it is often more proficient in generating the desired recombination results; and it is exponentially more cost effective, so almost any laboratory in the world can use it. CRISPR/Cas9 has been shown to work in several model organisms, and consequently researchers are keen to apply this technology for modifying genetic mutations in humans with uncured diseases as well as in human embryos, which arouses many scientific and ethical considerations.

Human embryonic gene editing

Genome editing technologies have come a long way and have already advanced towards mammalian models and clinical trials in humans. Recently, genetic modification of human embryos using CRISPR/Cas9 technology was achieved by the Huang laboratory in China in April 2015. They genetically modified un-viable embryos obtained from an in vitro fertilization clinic. These embryos were fertilized with two different sources of sperm, thus impairing their development. In this study, the Huang group repaired a mutation in the human -globin gene (HBB) that causes the blood disorder -thalassaemia. The CRISPR/Cas9 system and a donor DNA sequence containing the normal, healthy version of the HBB were injected into 86 embryos. A total of four embryos successfully integrated the corrected version of the HBB at the appropriate site. However, the authors reported a high number of off-target effects, meaning that CRISPR/Cas9 modified other locations in the genome; a non-ideal situation that could cause the disruption of other essential gene functions. The study demonstrated two important findings: genetic engineering is possible in human embryos and the CRISPR/Cas9 system requires essential improvements before it can be used in future studies on human embryos. More importantly, these results force scientists to question the future and the implications of such a powerful technology. Should we accept genetic engineering of human embryos? If yes, when and in what capacity should we accept it?

Current guidelines and regulation

Scientists in the United States are addressing the need for regulation of human embryonic gene editing. On April 29th, the US National Institute of Health (NIH) director, Dr. Francis Collins, released a statement emphasizing the bureaus policy against funding research involving genome editing of human embryos and the ethical concerns regarding this technology. However, the policy does not necessarily cover privately funded projects.

Safety regarding genetic engineering is a major concern and Huangs publication highlights this point. However, this publication forces the community to address whether scientists should use non-viable or discarded embryos to improve the efficiency and efficacy of the CRISPR/Cas9 system. The CRISPR/Cas9 system was developed for human genome targeting in 2012 and since then has seen rapid improvements. If it is decided that unviable embryos can be used for this type of research, the next step for US lawmakers is to evaluate new guidelines for the funding and safety of genetic engineering in these embryos.

Ethical concerns

While the interest and use of CRISPR/Cas9 has exploded since its discovery in 2012, prominent scientists in the field have already initiated conversations regarding the ethical implications that arise when modifying the human genome. Preventing genetic diseases by human genetic engineering is inevitable. The slippery slope is when/if we start to use it for cosmetic changes such as eye color or for improving a desired athletic trait. A perfect example is surgery, which we have performed for hundred years for disease purposes and is now widely used as a cosmetic tool. Opening the doors for genetic engineering of human embryos could with time lead to manipulate genetics for desirable traits, raising the fear of creating a eugenic driven human population.

Who are we to manipulate nature? However, for all those who suffer from genetic diseases the answer is not so simples; if we can safely prevent severe genetic diseases and create healthy humans, why not manipulate nature? Have we not already done this in other animal populations? At this time the long term effects of genome editing remain unknown, raising additional questions. As the field progresses, with appropriate regulations and guidelines it will eventually co-exist alongside other major controversial topics including nuclear power and genetically modified organisms. Since ethics are different across the world, creating international guidelines will be a challenge, but a necessity. Strict regulations are in place for nuclear power, the same should be possible for genetic engineering of human embryos. To outlaw genetic engineering entirely will be potentially declining a place at the discussion table, as the further utilization of CRISPR/Cas9 technology is unlikely to be abandoned.

This fall The National Academy of Sciences and National Academy of Medicine, together with CRISPR/Cas9 discoverers Dr. Jennifer Doudna, Dr. Emmanuelle Charpentier, and other leading scientist within the field are organizing an international summit to consider all aspects (both ethical and scientific) of human genetic engineering to develop standard guidelines and policies for practicing human genome editing. The NIH already has guidelines in place, and will potentially add more as a result of this summit. It is expected that other countries will have varying guidelines for human genomic engineering. Also, to avoid fear and misunderstanding, scientists will need to convey human genome editing in a responsible manner to the general human population. This summit is a step in the right direction encouraging caution and regulations. Hence, there is now a need for a timely but thoughtful set of guidelines for the general scientific community as well as for the broader human community.

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