Monthly Archives: April 2017

Gene therapy and genetic engineering are two closely related technologies that involve altering the genetic material of organisms. The distinction between the two is based on purpose. Gene therapy seeks to alter genes to correct genetic defects and thus prevent or cure genetic diseases. Genetic engineering aims to modify the genes to enhance the capabilities of the organism beyond what is normal.

Ethical controversy surrounds possible use of the both of these technologies in plants, nonhuman animals, and humans. Particularly with genetic engineering, for instance, one wonders whether it would be proper to tinker with human genes to make people able to outperform the greatest Olympic athletes or much smarter than Einstein.

We use the phrase genetic engineering more narrowly for the kind of alteration that aims at enhancement rather than therapy. We use the term gene therapy for efforts to bring people up to normalcy and genetic engineering or enhancement genetic engineering for efforts to enhancement peoples capabilities beyond normalcy.

There are several options for what kind of change to make to the gene. DNA in the gene could be replaced by other DNA from outside (called homologous replacement). Or the gene could be forced to mutate (change structure selective reverse mutation.) Or a gene could just be added. Or one could use a chemical to simply turn off a gene and prevent it from acting.

There are also several options for how to spread the genetic change to all the cells that need to be changed. If the altered cell is a reproductive cell, then a few such cells could be changed and the change would reach the other somatic cells as those somatic cells were created as the organism develops. But if the change were made to a somatic cell, changing all the other relevant somatic cells individually like the first would be impractical due to the sheer number of such cells. The cells of a major organ such as the heart or liver are too numerous to change one-by-one. Instead, to reach such somatic cells a common approach is to use a carrier, or vector, which is a molecule or organism. A virus, for example, could be used as a vector. The virus would be an innocuous one or changed so as not to cause disease. It would be injected with the genetic material and then as it reproduces and infects the target cells it would introduce the new genetic material. It would need to be a very specific virus that would infect heart cells, for instance, without infecting and changing all the other cells of the body. Fat particles and chemicals have also been used as vectors because they can penetrate the cell membrane and move into the cell nucleus with the new genetic material.

Genetic engineering to enhance organisms has already been used extensively in agriculture, primarily in genetically modified (GM) crops (also known as GMO --genetically modified organisms). For example, crops and stock animals have been engineered so they are resistant to herbicides and pesticides, which means farmers can then use those chemicals to control weeds and insects on those crops without risking harming those plants. In the future genetic enhancement could be used to create crops with greater yields of nutritional value and selective breeding of farm stock, race horses, and show animals.

Genetically engineered bacteria and other microorganisms are currently used to produce human insulin, human growth hormone, a protein used in blood clotting, and other pharmaceuticals, and the number of such compounds could increase in the future.

Enhancing humans is still in the future, but the basic argument in favor of doing so is that it could make life better in significant ways by enhancing certain characteristics of people. We value intelligence, beauty, strength, endurance, and certain personality characteristics and behavioral tendencies, and if these traits were found to be due to a genetic component we could enhance people by giving them such features. Advocates of genetic engineering point out that many people try to improve themselves in these ways already by diet, exercise, education, cosmetics, and even plastic surgery. People try to do these things for themselves, and parents try to provide these things for their children. If exercising to improve strength, agility, and overall fitness is a worthwhile goal, and if someone is praised for pursuing education to increase their mental capabilities, then why would it not be worthwhile to accomplish this through genetics?

Advocates of genetic engineering also see enhancement as a matter of basic reproductive freedom. We already feel free to pick a mate partly on the basis of the possibility of providing desirable children. We think nothing is wrong with choosing a mate whom we hope might provide smart, attractive kids over some other mate who would provide less desirable children. Choosing a mate for the type of kids one might get is a matter of basic reproductive freedom and we have the freedom to pick the best genes we can for our children. Why, the argument goes, should we have less freedom to give our children the best genes we can through genetic enhancement?

Those who advocate making significant modification of humans through technology such as genetic engineering are sometimes called transhumanists.

The danger objection points out that a few recent attempts at gene therapy in clinical trials have made headlines because of the tragic deaths of some of the people participating in the trials. It is not fully known to what extent this was due to the gene therapy itself, as opposed to pre-existing conditions or improper research techniques, but in the light of such events some critics have called for a stop to gene therapy until more is known. We just do not know enough about how gene therapy works and what could go wrong. Specific worries are that

The discrimination objection is as follows. Some people who are physically, mentally, or emotionally impaired are so as the result of genetic factors they have inherited. Such impairment can result in disablement in our society. People with disabilities are often discriminated against by having fewer opportunities than other people. Be removing genetic disorders, and resulting impairment, it is true that gene therapy could contribute to removing one of the sources of discrimination and inequality in society. But the implicit assumption being made, the objection claims, is that people impaired through genetic factors need to be treated and made normal. The objection sees gene therapy as a form of discrimination against impaired people and persons with disabilities.

The irrelevance objection is that gene therapy on reproductive cells may in some cases already be superceded by in-vitro fertilization and selection of embryos. If a genetic disorder is such that can be detected in an early embryo, and not all embryos from the parent couple would have it, then have parents produce multiple embryos through in-vitro fertilization and implant only those free from the disorder. In such a case gene therapy would be unnecessary and irrelevant.

Following are some other important objections:

Gene therapy is becoming a reality as you read this. Genetic engineering for enhancement is still a ways off. Plenty of debate is sure to occur over both issues.

Read the rest here:
Gene Therapy and Genetic Engineering - University of Missouri

IBS Center for Genome Engineering Director Kim Jin-Soo was recognized for his work on making CRISPR-Cas9 technology more precise and stable.

Asian Scientist Newsroom | April 12, 2017 | Top News

AsianScientist (Apr. 12, 2017) - Professors Kim Jin-Soo and Han Duck-Jong have been honored with the 10th ASAN Award in Basic Medicine and Clinical Medicine, respectively. The ASAN Award for Young Medical Scientists went to Professor Choi Jung-Kyoon at the Department of Bio and Brain Engineering at KAIST and Professor Ahn Jung-Min at the Department of Cardiology at the University of Ulsan College of Medicine.

The basic and clinical medicine winners each received 300 million won (~US$262,000) while the Young Medical Scientists received 50 million won (~US$44,000) at an awards ceremony held on March 20, 2017.

The ASAN Award in Medicine was established in 2007 by the ASAN Foundation to discover and encourage medical scientists who have achieved remarkable accomplishments in the fields of basic and clinical medicine.

Kim, who is the Director of the Institute for Basic Science Center for Genome Engineering, was recognized for his work on making the CRISPR-Cas9 gene editing system more precise and stable.

Using genome editing techniques, I'd like to focus on research which is helpful for patients with genetic and degenerative diseases as well as cancer that are considered intractable. I'll strive harder to develop and commercialize treatments that can directly help such patients, he said.

This honor is largely attributed to the dedicated researchers who have worked with me. I see this award as encouragement for me to contribute to society and humanity by devoting myself more to research.

Source: Institute for Basic Science; Photo: ASAN Foundation. Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

View original post here:
Gene Editing Researcher Receives ASAN Award In Basic Medicine - Asian Scientist Magazine

National Institutes of Health (press release)

Study finds genetic basis for drug response in childhood absence epilepsy National Institutes of Health (press release) A team led by Tracy A. Glauser, M.D., director of the Comprehensive Epilepsy Center at Cincinnati Children's Hospital Medical Center and professor of pediatrics in the University of Cincinnati College of Medicine, investigated whether there may be a ... and more »

Follow this link:
Study finds genetic basis for drug response in childhood absence epilepsy - National Institutes of Health (press release)

April 12, 2017 by Anna Williams The top row indicates mice with glioblastoma controlled for tumor size. The bottom row shows their expression of MGMT, a protein that makes tumor cells more resistant to chemotherapy. The left is a control, while the right shows significantly decreased levels of MGMT after treatment with the nanoparticles. Credit: Northwestern University

Northwestern Medicine scientists have developed a novel testing platform to assess, in real time, the efficacy of nanomaterials in regulating gene expression. The findings, published in Proceedings of the National Academy of Sciences, could help to facilitate preclinical investigations and optimize nanotherapeutics for cancers before they reach clinical trials.

Timothy Sita, a seventh-year MD/PhD student in the Medical Scientist Training Program, was the first author of the study, which looked at the platform in animal models.

"This is an important step forward for the field," said principal investigator Alexander Stegh, PhD, assistant professor of Neurology and of Medicine. "The very thorough optimization that we see in conventional drug development had been missing in the nanotech space, and we felt very strongly about changing this. The system that we developed here really allows us to support those efforts, and evaluate our nanoparticles in the most relevant models, in an in vivo setting."

Chad Mirkin, PhD, the George B. Rathmann Professor of Chemistry in theWeinberg College of Arts and Sciences and a professor of Medicine in the Division of Hematology/Oncology, was also a corresponding author of the paper.

The scientists demonstrated the concept while using nanostructures called spherical nucleic acids (SNAs) to target a resistance factor gene in glioblastoma, an aggressive, incurable type of brain tumor.

SNAs, first developed by Mirkin at Northwestern in 1996, consist of dense strands of RNA packed around a nanoparticle core. Because of their unique properties, SNAs are capable of both crossing the blood-brain barrier and entering into tumor cells, where they can directly target gene activity that encourages cancer growth.

While these conjugates are a promising tool in the era of precision medicine, scientists previously lacked a quantitative method to assess how SNAs regulated gene activity in living organisms, which would provide new insights into how to optimize the therapies.

"We've seen that these particles can basically target any cancer gene, but we didn't know when they worked best or what dosing regimens to use," Sita said. "As such, preclinical trials weren't as successful as they could have been."

In the current study, the scientists showed that by using a type of non-invasive imaging on the mice, they could gauge in real time how the nanoparticles affected levels of an intratumoral target protein.

"Now we can tweak these particlesplay with the shape of the nanoparticle, or how much RNA we load onto the particle, for exampleand then assess very quickly whether those changes are more effective or not," Sita explained. "It's a platform to help optimize the drugs in mice before they go to human trials, and make something that will translate better to the clinic."

While the method could be generalizable to investigating nanotherapeutics for many types of cancers, the study also has clinical implications unique to glioblastoma.

The scientists developed nanoparticles to knock down O6-methylguanine-DNA methyltransferase (MGMT)a protein which reduces the impact of chemotherapyin mice with glioblastoma. Through the imaging platform, they discovered that mice had the lowest levels of the protein between 24 to 48 hours after receiving the nanoparticles, suggesting the optimal time to administer chemotherapy.

"We showed a very significant reduction in tumor volume when we combined these particles with the chemotherapy," Sita said. "By silencing this gene that's causing resistance to the chemotherapy, we can have a much more profound response. That's the key clinical angle."

Explore further: Cancer genes deactivated in deadly brain cancer

More information: Timothy L. Sita et al. Dual bioluminescence and near-infrared fluorescence monitoring to evaluate spherical nucleic acid nanoconjugate activity in vivo, Proceedings of the National Academy of Sciences (2017). DOI: 10.1073/pnas.1702736114

Northwestern Medicine scientists have identified a small RNA molecule called miR-182 that can suppress cancer-causing genes in mice with glioblastoma mulitforme (GBM), a deadly and incurable type of brain tumor.

Glioblastoma multiforme (GBM), the brain cancer that killed Sen. Edward Kennedy and kills approximately 13,000 Americans a year, is aggressive and incurable. Now a Northwestern University research team is the first to demonstrate ...

Northwestern University's Chad A. Mirkin, a world-renowned leader in nanotechnology research and its application, has invented and developed a powerful material that could revolutionize biomedicine: spherical nucleic acids ...

The University of Delaware's Emily Day is a part of a team of researchers that has developed a nanotherapeutic capable of penetrating the blood-brain barrier.

A new high-tech but simple ointment applied to the skin may one day help diabetic patients heal stubborn and painful ulcers on their feet, Northwestern University researchers report.

A research team led by Northwestern University nanomedicine expert Chad A. Mirkin and Sergei Gryaznov of AuraSense Therapeutics is the first to show spherical nucleic acids (SNAs) can be used as potent drugs to effectively ...

When you charge a battery, or when you use it, it's not just electricity but also matter that moves around inside. Ions, which are atoms or molecules that have an electric charge, travel from one of the battery's electrodes ...

University of Arkansas researchers have discovered a simple and scalable method for turning graphene oxide into a non-flammable and paper-like graphene membrane that can be used in large-scale production.

Northwestern Medicine scientists have developed a novel testing platform to assess, in real time, the efficacy of nanomaterials in regulating gene expression. The findings, published in Proceedings of the National Academy ...

A new atomically thin material similar to graphene has been proven to be a promising new superconductive material.

For the lithium-oxygen battery system, it is well recognized the charging and discharging reaction produces peculiar reaction product shapes that resemble doughnuts and balloons. Yet, how these shapes form has remained a ...

(Phys.org)U.K.-based Surrey Nanosystems has announced that it has improved on the original Vertically Aligned Nanotube Array BLACK (Vantablack coating) which the company claimed to be the blackest material ever made. The ...

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Read more:
Scientists develop platform to investigate therapeutic nanomaterials - Phys.Org

REDWOOD CITY, CA--(Marketwired - Apr 12, 2017) - CardioDx, Inc., a molecular diagnostics company specializing in cardiovascular genomics, announced today the publication of results from the multi-center, community-based PRESET Registry in the peer-reviewed journal, The American Journal of Medicine.1 The study results provided further confirmation of the clinical utility of the Corus CAD test to help clinicians in real-world practice determine if their patients' symptoms are due to a blockage in the heart arteries, and if referral to cardiology or to advanced cardiac testing was necessary.Previously validated with a 96% negative predictive value and 89% sensitivity, the Corus CAD test is a precision medicine blood test that integrates age, sex, and gene expression levels into a single score indicating the current likelihood of a significant narrowing or blockage in the coronary arteries, also known as obstructive* coronary artery disease (CAD).

The PRESET Registry (NCT01677156, clinicaltrials.gov) demonstrated that patients with low Corus CAD scores (defined as 15) were less likely to undergo cardiac referral, were unlikely to have positive findings on further cardiac work-up, and had a low rate of adverse cardiovascular events at one year follow-up.

Every day, approximately 8,000 patients present to primary care clinics with signs and symptoms of obstructive CAD. Yet, a review of published patient data suggests that only 10% of patients presenting with chest pain to primary care clinicians for evaluation are actually found to have CAD. The majority of chest pain symptoms are caused by non-cardiac sources such as heartburn, muscle spasm, anxiety, or lung-related conditions.2

"The PRESET Registry provides doctors and patients with further evidence that, as a first-line assessment tool for patients with symptoms suggestive of CAD in outpatient clinics, the age, sex, and gene expression score (Corus CAD) can safely and reliably help clinicians direct cardiac care," said Joseph A. Ladapo, Assistant Professor, Division of General Internal Medicine and Health Services Research, David Geffen School of Medicine at University of California at Los Angeles. "Patients with low scores were less likely to undergo further cardiac evaluation and testing, and this saves some patients from being unnecessarily exposed to the risks of cardiac procedures and radiation from cardiac nuclear imaging, along with the costs associated with pursuing advanced cardiovascular testing."

The primary objective of the study was to evaluate the clinical utility or impact of the Corus CAD test on medical decision-making, specifically cardiac referrals. Results demonstrated that patients with low Corus CAD scores ( 5) had an 85% decreased odds of referral for further cardiac evaluation or testing versus elevated Corus CAD scores ( > 15). Only 10% of patients with low Corus CAD test scores versus 44% of elevated scoring patients were referred by clinicians to cardiology or for advanced cardiac testing (unadjusted Odds Ratio (OR) = 0.15, p < 0.0001; adjusted OR after accounting for clinical covariates = 0.18, p < 0.001). Furthermore, when evaluating the Corus CAD score as a continuous variable from 1-40, the higher the Corus CAD score, the more likely the patient was to undergo cardiac referral. Major adverse events and revascularization were noted in 1.2% (3/252) of patients with low Corus CAD scores and 4.5% (14/314) of patients with elevated Corus CAD scores (p < 0.03).

"The need for better cardiac care and safer tests has always been the goal of the Corus CAD test," said Mark Monane, MD, FACP, Chief Medical Officer of CardioDx. "The final analysis of the PRESET Registry showed that clinicians are integrating the Corus CAD test into real-world clinical decision-making to help risk stratify patients to the appropriate care pathway. Incorporating the Corus CAD test into the primary care setting provides an opportunity for patients, healthcare providers, and managed care payers to benefit, as expensive and potentially risky cardiac tests or procedures may be avoided in patients with low Corus CAD scores."

About the PRESET Registry The PRESET Registry (A Registry to Evaluate Patterns of Care Associated with the Use of Corus CAD in Real World Clinical Care Settings) assessed the effects of the Corus CAD score on clinical decision-making in stable non-diabetic patients without a history of obstructive CAD. The analysis included patients from 21 primary care practices from the time period of September 2012 through August 2014. This final endpoint analysis included 566 patients with typical or atypical symptoms suggestive of obstructive CAD and one-year follow-up post-Corus CAD testing.

Read More

About Obstructive Coronary Artery Disease Coronary artery disease (CAD) is a very common heart condition in the United States. One in seven deaths among Americans is caused by CAD.3 CAD can cause a narrowing or blockage of the coronary arteries (vessels to the heart that supply the heart with blood, oxygen, and nutrients), reducing blood flow to the heart muscle. This narrowing or blockage in the coronary arteries is often referred to as obstructive CAD, characterized by the presence of atherosclerosis, or plaque.

About the Corus CAD Test Corus CAD is the first and only commercially available blood test that can safely and conveniently help primary care clinicians and cardiologists assess whether or not a stable non-diabetic patient's symptoms may be due to obstructive coronary artery disease. The test incorporates age, sex and gene expression measurements into a single score that indicates the likelihood of obstructive CAD. Clinicians use the Corus CAD score, along with other clinical information, to determine whether further cardiac testing is necessary, which can help patients avoid unnecessary exposure to radiation associated with medical imaging testing, as well as possible reactions to imaging dyes and/or potential complications from invasive cardiac tests requiring catheterization. The test involves a routine blood draw that is conveniently administered in the clinician's office. The Corus CAD test is the only sex-specific test for the evaluation of obstructive CAD because it accounts for cardiovascular differences between men and women.

The test has been clinically validated in independent male and female patient cohorts, including two prospective, multicenter U.S. studies, PREDICT and COMPASS.4,5 In the COMPASS study, the Corus CAD test outperformed myocardial perfusion imaging (MPI) as a diagnostic tool to exclude obstructive CAD by demonstrating a higher negative predictive value (96% vs. 88%, p < 0.001) than MPI for assessing the presence of obstructive CAD.6 To date, over 220,000 Corus CAD test results have been provided to clinicians. CardioDx processes all Corus CAD test samples at its CLIA-certified and CAP-accredited clinical laboratory in Redwood City, California.

The Corus CAD test has been recognized by The Wall Street Journal's Technology Innovation Awards, honored as a Gold Edison Award recipient, and named one of TIME's Top 10 Medical Breakthroughs.

About CardioDx CardioDx, Inc., a molecular diagnostics company specializing in cardiovascular genomics, is committed to developing clinically validated tests that empower clinicians to better tailor care to each individual patient. Strategically focused on coronary artery disease, CardioDx is committed to expanding patient access and improving healthcare quality and efficiency through the commercialization of genomic technologies. Please visit http://www.cardiodx.com for additional information.

For media inquiries, please contact Glenn Silver of Lazar Partners, +1-212-871-8485, gsilver@lazarpartners.com.

* Obstructive CAD is defined as at least one atherosclerotic plaque causing 50% luminal diameter stenosis in a major coronary artery (1.5 mm lumen diameter) as determined by invasive quantitative coronary angiography (QCA) or coronary computed tomography angiography (CTA) (2.0 mm).

1 Ladapo JA, Budoff M, Sharp D, et al. Clinical Utility of a Precision Medicine Test Evaluating Outpatients with Suspected Obstructive Coronary Artery Disease.Am J Med. 2017;130(4):482.e11-482.e17. 2 Cayley WE Jr. Diagnosing the Cause of Chest Pain. Am Fam Physician. 2005;72(10);2012-2021. 3 Mozaffarian D, Benjamin EJ, Go AS, et al. On Behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics - 2016 Update: A Report from the American Heart Association. Circulation. 2016;133(4):e38-e360. 4 Rosenberg S, Elashoff MR, Beineke P, et al. Multicenter Validation of the Diagnostic Accuracy of a Blood-Based Gene Expression Test for Assessing Obstructive Coronary Artery Disease in Nondiabetic Patients. Ann Intern Med. 2010;153:425-434. 5 Thomas GS, Voros S, McPherson JA, et al. A Blood-Based Gene Expression Test for Obstructive Coronary Artery Disease Tested in Symptomatic Nondiabetic Patients Referred for Myocardial Perfusion Imaging: The COMPASS Study. Circ Cardiovasc Genet. 2013;6(2):154-162. 6 The COMPASS study demonstrated that the Corus CAD algorithm has an NPV of 96% at the pre-specified threshold of 15 in a population of men and women referred to MPI.

Original post:
New Study Published in The American Journal of Medicine Expands the Clinical Evidence Underscoring the Value of ... - Yahoo Finance