Category Archives: Gene Medicine

Some farsighted (or just plain lucky) investors bought shares of Tesla Motors (NASDAQ: TSLA) early on. They took a huge risk, but that risk paid off. Tesla stock is up nearly 1,400% since the company went public in 2010.

Stocks like Tesla are a pretty rare species. And they're not always easy to spot early on. But some are still out there. One stock that is in its infancy right now that could be a huge winner in the next few years is gene-editing pioneerEditas Medicine (NASDAQ: EDIT). Could Editas be the Tesla of healthcare?

Image source: Getty Images.

Tesla wasn't the first automaker to create an electric car. The first electric car in the U.S. dates back to 1890. However, Tesla did introduce a new-and-improved version of the electric car that captured the attention of consumers.

Likewise, Editas isn't the first biotech to use gene editing -- the insertion, deletion, or replacement of DNA in a cell or organism. Others have been working on developing drugs using gene-editing techniques for a long time before Editas was formed. Sangamo Therapeutics (NASDAQ: SGMO), for example, got its start in 1995 and has been researching potential applications of gene-editing therapies ever since.

But like Tesla, Editas has a new-and-improved approach to an idea that's been around awhile. Sangamo uses a gene-editing method called zinc finger nuclease (ZFN) technology. ZFN was introduced in the early 1990s. Editas uses the CRISPR-Cas9 gene editing approach, which wasn't discovered until around five years ago.

CRISPR-Cas9 has several advantages over older gene-editing technologies. As was the case with Tesla's cars compared to previous electric cars, CRISPR-Cas9 is better and faster than the alternative methods for editing genes. It's easier to build, and it can modify DNA with greater precision. And CRISPR-Cas9 is cheaper as well (something Tesla hasn't been able to claim until recently).

Some think only of electric cars when they think about Tesla. The reality, though, is that Tesla's vision is much bigger than electric cars: Its plan is to promote sustainable energy sources in all areas of life.

It's also possible to look at Editas in a narrow way. The biotech's pipeline currently includes seven pre-clinical programs. One of those programs is a collaboration with Juno Therapeutics (NASDAQ: JUNO) to use gene editing in engineering T cells to fight cancer. Editas' lead program EDIT-101 targets treatment of rare genetic eye disease Leber Congenital Amaurosis type 10. The company plans to submit an Investigational New Drug (IND) application for EDIT-101 next year.

Image source: Getty Images.

There's a much bigger potential for Editas than just those few programs, though. The company has licensed exclusive rights to patents for the use of CRISPR-Cas9 in editing eukaryotic cells (i.e., any cells with a nucleus, including all human and animal cells). Editas also licensed patents to another type of gene editing, CRISPR-Cpf1, that could be even better than CRISPR-Cas9 for some mutations.

What does this mean for Editas' potential? There are around 6,000 diseases caused by genetic mutations. Over 95% of them don't have an approved therapeutic alternative. Even where there are approved therapies, they often only treat the symptoms of the disease. CRISPR-Cas9 and CRISPR-Cpf1 hold the potential to be used to treat many of these genetic diseases, particularly those affecting bone marrow, eyes, liver, lung, and muscle. Editas will be a go-to partner for many biopharmaceutical companies wanting to target those diseases.

Allergan (NYSE: AGN) became the first big pharma company to join forces with Editas earlier this year. The two companies are working together to develop gene-editing drugs for several eye disorders. This deal also allows Allergan to license Editas' lead program, EDIT-101.

It's not an exaggeration to speculate that Editas Medicine's potential could be greater than Tesla's if Editas' gene-editing technology helps cure a range of serious diseases. However, at this point, it would be only speculation. None of Editas' programs have even reached clinical trials yet. The odds of any program making it all the way to approval are low -- less than 10% based on the Food and Drug Administration's analysis of all experimental drugs.

There's also the possibility that even better gene-editing techniques will be discovered. That wouldn't derail Editas' efforts -- after all, Sangamo continues to move forward with ZFN even though the technology has been eclipsed by CRISPR. However, a gene-editing approach that proved to be better than CRISPR would probably drastically reduce the appeal of Editas as a partner for larger companies wanting to develop treatments for genetic diseases.

Editas could truly be the Tesla of healthcare. For now, though, the key word in that statement -- "could" -- is future tense.

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This Stock Could Be the Tesla of Healthcare - Madison.com

Sequencing genomes to diagnose puzzling symptoms presents a conundrum: how to interpret whether a persons genotype causes the syndrome without comparison to many other human genome sequences? Put another way, a gene variant (mutation) that people with the same symptoms share must also be absent in people without the syndrome for it to be labeled causal, rather than the disturbingly vague variant of uncertain significance.

The challenge is in de-identifying the hordes of healthy genomes needed to add diagnostic context to those with disease-causing mutations. A team of biologists, computer scientists, and cryptographers at Stanford University described in Sciencemagazine a new computational tool to make certain that genomic discrimination doesnt happen, according to co-author Gill Bejerano, PhD, associate professor of developmental biology, pediatrics, and computer science.

A genome sequence can reveal much more than the needle-in-the-haystack mutations that might underlie a diagnosis: parentage, ancestry, susceptibilities and risk factors, even whether a certain drug will work, binge-drinking make you violently ill, or smoking likely to cause lung cancer. How can genome sequencing provide useful information without sacrificing privacy?

THE CLASSIC GYMREK STUDY

One of my favorite papers is also from Science, Identifying Personal Genomes by Surname Inference,if you can call a report from 2013 a classic. First author was then-grad student Melissa Gymrek, who now heads a lab at UCSD.

Gymrek and her co-workers tackled the 1000 Genomes Project, which ran from 2008-2015 and spawned a supposedly anonymous database. The informed consent form read, . . . it will be hard for anyone to find out anything about you personally from any of this research.

Right. Online searches easily shattered that premature promise of privacy.

Gymrek, then a student of Yaniv Erlich, a researcher at the Whitehead Institute who had worked with databases at financial banks, tried to identify people whod anonymously donated DNA to the 1000 Genomes Projectjust to see if they could.

They looked at sets of short tandem repeats, the bits of sequence of 2-13 DNA bases used in forensics and genetic genealogy to distinguish individuals. Consulting public genealogy databases they found surnames corresponding to specific Y haplotypes (STRs linked on the male chromosome).

Basic public information such as state of residence and birth year was easy to find. DNA data posted on family websites confirmed some identifications. The researchers found women by cross-referencing DNA sequences in the Coriell Cell Repositories in New Jersey to other data. Searching mutation databases for disease, hometown, and date of birth identified children.

When Gymrek had identified 50 people fairly easily, Dr. Erlich, alarmed, notified the NIH, catalyzing efforts to begin to hide some of the DNA data, although of course they couldnt control people whod post anything on social media. Their report in Science became a rallying cry of sorts for the ease of assigning names to DNA sequences something thats much easier today, with more than a million of our genomes sequenced and with the ability to carry such information on our smartphones.

THREE COMPELLING EXAMPLES

In the new paper, the researchers used a cryptographic approach called Yaos protocol with cloud computing to enable a genome peruser to zero in on the DNA sequences of clinical interest, while ignoring all else. Its a genomic cloaking device, for those familiar with the Romulan invention from Star Trek that makes a spaceship seem to vanish. It irked Captain Kirk.

Aterrific news releaseby Krista Conger at Stanford explained it all:

Using the technique, the researchers were able to identify the responsible gene mutations in groups of patients with four rare diseases; pinpoint the likely culprit of a genetic disease in a baby by comparing his DNA with that of his parents; and determine which out of hundreds of patients at two individual medical centers with similar symptoms also shared gene mutations. They did this all while keeping 97 percent or more of the participants unique genetic information completely hidden from anyone other than the individuals themselves, the release said.

Many news aggregators just publish news releases verbatim, but I dug a little deeper:

For the four already-known diseases, the technique identified 211-374 rare functional gene variants in 210- 356 genes (meaning more than one mutation in some genes) among the patients, then selected the most likely candidates. The computation correctly identified the mutation in all four across all 20,663 genes, and in 5 to 10 seconds. Anyone who reads this blog regularly knows that a diagnostic odysseyfor a rare genetic disease can take years, using conventional medicine.

The baby was XY (chromosomally male) with female genitalia. The child and the parents each had 164-185 rare functional variants found with exome sequencing, and the computation revealed only two unique to the child. A review of the genetics literature found that one, ACTB, made sense and it had been found in the 1000 Genomes Project! Only the two meaningful variants were reported to the parents and their provider, leaving what the researchers call a protection quotient of 99.6%. (Definition: the fraction of private information that is exposed neither to the other participants nor to the entity running the computation.)This more complex test took just under an hour.

The researchers compared 928 patients from one medical center to 282 patients at another, generating a list of 5,000+ rare functional variants seen in at least one patient, then whittled it down to 159 variants seen among patients in both hospitals. The info diagnosed patients with specific heart problems, and also revealed previously unrecognized gene-disease connections so the computation is a discovery tool too.

BENEFITS TO GENOME CLOAKING

The beauty of the technique, and the secret to the privacy promise, is that the patient enters the data, into smartphone, tablet, or computer. That shouldnt sound scary, for we send our info into the ether all the time, from ordering concert tickets to making plane reservations. In this way, no person or computer, other than the individuals themselves, has access to the complete set of genetic information, said Dr. Bejerano.

The computation encrypts a genome sequence into a linear series of values that rates each gene variant according to several criteria well-established among genome researchers:

Could the genes function explain a patients symptoms?

Is the variant rare? This is where the need for a backup million or so sequenced genomes comes in. If a variant is common, it cant be making people too sick to reproduce.

Is the variant functional? What does it do?

The direct involvement of the patient and the return of only relevant data from the cloud can avoid the genetic red flags that might underlie denial of a loan or life insurance, neither protected under the Genetic Information Nondiscrimination Act (GINA), should it survive the Trump administration. And the data from the healthy genomes is aggregated without identifiers.

Genome cloaking at some point requires interpretation of and communication by health care providers who are familiar and comfortable with DNA information. That might still be a rare breed. Heres a quick test that I just invented for a provider discussing genetic testing: define SNP, CNV, VUS, and exome. If she or he cant, find a genetic counselorpronto. The medias common depiction of physicians as scientists the Dana Scully effect, from the X-Files doctor constantly calling herself a scientist can set up unrealistic expectations of expertise.

Another advance that could come from genome cloaking would be, finally, the ability to track sets of genes. This is important because gene actions can oppose. Whats the use of finding out you have a gene variant that increases the risk of Alzheimers, like APOE e4, yet not knowing that you also inherited a gene variant that lowers the risk (APOE e2)?

With the ability to nail disease-causing gene variants, while offering the privacy that Melissa Gymreck showed years ago to be easily compromised, genome cloaking may be able to catapult DNA science into the research lab and clinic, by providing reassurance to both families with genetic disease and to the healthy population whose genome sequences are vital to providing context.

(Thanks to NHGRI for images.)

Read the original here:
Genome Cloaking Preserves Privacy While Enabling Diagnosis ... - PLoS Blogs (blog)

People often ditch statins due to side effects

GARO/PHANIE/REX/Shutterstock

By Viviane Callier

Should you take statins? The common drugs are a safe and effective way to lower cholesterol and prevent heart disease, but many of those taking them give up due to painful side effects. Furthermore, in some people, this pain may be caused by the nocebo effect, rather than the drug itself. But genetic screening could help reduce side effects and reassure people they are unlikely to feel any pain, encouraging more people to take statins.

Deepak Voora of Duke University, North Carolina, and his colleagues have been researching a gene associated with muscle pain in people taking statins. The gene encodes a protein that carries drugs into liver cells. A variant of this gene has been linked to aches in response to statins.

To find out if this variant affects what side effects someone experiences from different statins, Voora and his team reanalysed data from a clinical trial that had randomly assigned three types of this drug. They found that people with the gene variant had the highest risk of side effects when they were given a statin called simvastatin, but this risk was much lower when they took pravastatin.

The researchers then ran a trial in 159 people to see if genetic screening could help prescribe the most appropriate statin for each person. All the participants had previously stopped taking statins due to muscle pain.

First, everyone was given a genetic test, but only one group were told their results. For this group, a doctor explained whether or not their DNA put them at risk of statin-related muscle pain. Those at risk were recommended a statin that was less likely to cause side effects for their genetic variant, while those not at risk were told they could try any type.

The other participants werent told their test results, and instead received standard, generic recommendations from their doctor.

Of those told their results, around 57 per cent decided to start taking statins again within the next three months, compared with only a third of those who received generic recommendations. By the end of the eight-month study, those who knew their results had blood LDL cholesterol levels that were, on average, 10 to 15 per cent lower than the others.

Thats pretty remarkable given these were patients that were initially refusing to take statins, says Jason Vassy of Harvard Medical School.

By improving a persons perception of a drug, you can boost how many take it and keep taking it, which has been a major problem, says Voora. He hopes the approach could be extended to help doctors and patients feel more confident about other drugs. This concept of using precision medicine to address the psychology of how patients feel about drugs might be a winning combination, he says.

Read more: Statin muscle aches are all in my head? I beg to differ

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Genetic test helps people avoid statins that may cause them pain - New Scientist

Once difficult and expensive even for the most technologically advanced labs, genetic testing is fast becoming a cheap and easy consumer product. With a little spit and 200 dollars, you can find out your risk for everything from cystic fibrosis to lactose intolerance.

But its important to remember that not all genetic tests are created equal. And even the best clinical genetic test, carried out in a medical lab under a doctor's supervision, isn't perfectgenes are important, but they don't seal your fate.

Genetic tests are diagnostic, so anyone who is curious about their health can get one done. But they're more informative if you think you might be at risk for a genetic disorder.

Heavy-duty genetic tests have been used as a clinical tool for almost half a centurylong before 23andMe and Ancestry.com began offering direct-to-consumer tests. Lets say that many women in your family have had breast cancer. You can get a genetic test to see if you may have inherited an abnormal version of the BRCA gene, known to increase your risk for breast cancer.

Heidi Rehm, associate professor of pathology at Harvard Medical School, is the director of the Laboratory for Molecular Medicine, where patients get tested for diseases that can be traced to specific genetic roots. She says it is most common for people to get tested when they either suspect or know that they have a genetic disease; it may have affected multiple people in their family or they could show symptoms of something widely known to be genetic, like sickle cell anemia. For these people, genetic tests can provide a much-needed explanation for an illness and help doctors determine the best course of treatment. Babies are often tested for genetic diseases, either while they are still fetuses or shortly after birth.

Others get genetic tests if they and their partner both have family histories of an inherited diseaseeven if they dont have the disease themselves. For example, cystic fibrosis is linked to one particular gene, but you have to inherit the abnormal version of the gene from both your parents to get the disease. If you only inherit one copy, you may never knowyou wont display any of the symptoms. But if you and your partner both carry one copy of the faulty gene, your child could still inherit two copies. Genetic tests can forewarn you of that possibility.

But Rehm says there has been a recent trend of healthy people getting tested to predict whether theyll get certain diseases. I do think there are settings where predictive genetic testing is incredibly important and useful, Rehm says; for example, knowing that youre at risk for breast cancer gives you the opportunity for early intervention (remember when Angelina Jolie got a double mastectomy upon finding out she had a mutated BRCA gene?)

But Rehm also points out that genetic tests may not be as straightforward as they seem. For example, some genes are thought to increase risk of getting a certain disease, but it might only happen if you have specific family history, or you might be able to reduce your risk with lifestyle changes. So remember that a genetic test isnt the final verdictthere are other factors at play too.

Not entirelyits scope is limited. For starters, not all diseases are caused by genes. Plenty of conditions stem from environmental and lifestyle factors; they may interact with your genes, but the external factors are the real trigger.

But even if a disease is caused solely by faulty instructions written in your genes, you wont necessarily be able to test for it. Thats because genetic tests are mainly used for diseases that are penetrant, a term that scientists use to describe a strong connection between having a certain gene (or multiple genes) and getting a disease.

Genetic tests are surprisingly simple on the surface. All thats required of you is a small sample of cells, like a blood sample or saliva (which doesnt have DNA itself, but picks up cheek cells during its journey out of your mouth). It get sent to a lab where sequencing machines match up small pieces of synthetic DNA with your DNA to figure out the overall sequence.

Once they have your sequence, geneticists can compare it with "normal" or disease-causing sequences. In the end, they might give you a yes or no answer, or sometimes youll get a probabilitya measure of how much your genes increase your risk of developing the disease. Then, its up to your doctor to figure out what these genes (in combination with your lifestyle, family history and other risk factors) mean for your health.

With penetrant diseases, theres a very, very high ability to explain the disease, Rehm says. For example, the breast cancer-related gene BRCA1 can give you a 60 percent chance of getting breast cancer (in Jolies case, with her family history, the risk was 87 percent.)

This makes genetic tests better at detecting so-called rare diseases, says Steven Schrodi, associate research scientist at the Marshfield Clinic Research Institutes Center for Human Genetics, but theyre less useful when it comes to more common diseases, like heart disease or diabetes. Genetics can increase your likelihood of getting these disease, but scientists still dont know quite how much. Part of the problem is that there may be dozens or hundreds of genes responsible for these diseases, Schrodi says.

We have an incomplete understanding of why people get diseases, Schrodi says. A large part of it hinges on how we define diseases. Perhaps physicians have inadvertently combined multiple diseases together into a single entity.

Consumer genetic teststhe ones where you send in samples from homesometimes claim to test for these more complex traits, but be careful: Their results might not be very medically relevant, Rehm says. If they tell you that your genes make you twice as likely to develop diabetes, for example, that's a marginal increase that doesn't significantly affect your risk, especially when you take into account lifestyle factors.

Genes do seem to play a role in determining lifespan. After all, some family reunions stretch from great-great-grandparents all the way down to infants. Scientists have studied centenarianspeople who lived to be 100 years oldand found that people with certain versions of genes involved in repairing DNA tend to live longer.

This makes sense because aging leaves its mark on your DNA. Environmental factors can damage DNA, and even the routine chore of replicating cells can introduce errors as the three billion units of your DNA are copied over and over. Long-lived individuals have different sequences that seem to make their cells better at keeping DNA in mint condition.

But figuring out your expiration date is more complex than just testing for a few genes, says Jan Vijg, professor of genetics at Albert Einstein College of Medicine. In theory, you could design a test that looks at specific genes that might measure your risk for developing Alzheimers Disease or other age-related diseases, or your risk for aging quickly. To some extent, yes: Biomarkers will tell you something about your chances of living a long life, Vijg says. Still, that will only work if you live a careful life. And that means no accidents, infections, or cancers.

Aging also affects the exposed ends of your DNA, called "telomeres." DNA is stored as chromosomes, those X-like structures that you may have seen in biology textbooks. The most vulnerable parts of the chromosome are the chromosomes tips, which get shorter as you age because they arent properly replicated. But while telomere length might let you compare your DNA now with your DNA from a decade ago, you cant compare your own telomeres with other peoples telomeres. Theres a lot of variation between individuals, Vijg says. Some of us are just old souls (on the genomic level, that is.)

The methylation test, which looks at how the presence of small chemical groups attached to your DNA changes as you age, might be a better bet. A study at UCLA showed that changes were slower in longer-lived people. But Vijg is hesitant: I would not put my hopes on that as a marker to predict when exactly youre going to die.

For now, just enjoy your life, because you cant predict death. And if you decide to unlock the secrets of your DNA with an at-home test, don't take those results for more than their worth.

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What can genetic testing really tell you? - Popular Science

Could vitamin C help drugs fight leukaemia?

Steve Gschmeissner/SPL/Getty

By Aylin Woodward

Injections of vitamin C could be a way to help fight blood cancer. Experiments in mice suggest that the nutrient helps tell out-of-control cells to stop dividing and die.

Some blood cancers, including acute and chronic leukaemia, often involve mutations affecting a gene called TET2. This gene usually helps ensure that a type of stem cell matures properly to make white blood cells, and then eventually dies. But when TET2 mutates, these cells can start dividing uncontrollably, leading to cancer. Mutations in TET2 are involved in around 42,500 cancers in the US a year.

Luisa Cimmino and Benjamin Neel at the New York University School of Medicine and their colleagues have genetically engineered mice to have variable TET2 function. They found that a 50 per cent reduction in TET2 activity can be enough to induce cancer, but that TET2 activity needs to remain low if the disease is to continue developing. If we genetically restore TET2, it blocks unhealthy replication and kills the cells, says Cimmino.

Next, the team turned to vitamin C, because it is known to have an effect in embryonic stem cells, where it can activate TET2 and help keep cell replication in check.

The team injected mice with low TET2 activity with very high doses of vitamin C every day for 24 weeks and found that it slowed the progression of leukaemia. By the end of this period, a control group that got no injections had three times as many white blood cells a sign of pre-leukaemia.

When the team exposed human leukaemia cells in a dish to a cancer drug, they found they got better results when they added vitamin C.

Neel hopes that high doses of vitamin C will eventually be incorporated into cancer therapies. People who have acute myeloid leukemia are often of advanced age, and may die from chemotherapy. Vitamin C in combination with cancer drugs may provide an alternative approach.

But taking large amounts of vitamin C is unlikely to prevent you from getting cancer, says Neel. The mice were given 100 milligrams of vitamin C in each injection, the equivalent of about two oranges. But the average person weighs about 3000 times as much as a mouse. Because the body stops taking in the vitamin after around 500 milligrams, any therapies would need to supply vitamin C intravenously. You cant get the levels of it necessary to achieve the effects in this study by eating oranges, he says.

Journal reference: Cell, DOI: 10.1026/j.cell.2017.07.032

Read more: Choosing alternative cancer treatment doubles your risk of death

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Vitamin C helps genes to kill off cells that would cause cancer - New Scientist

The first reportof gene editing in viable human embryos performed in the United Stateshas beenpublished. The landmark study demonstrates that gene editing technology can successfully repair faulty genes in the human germline a scientific term that refers to sperm or egg cells, zygotes, and embryos.

Correcting gene mutations in the germline is powerful because any such modifications are inherited by subsequent generations in a fixed, self-perpetuating configuration. To many, this represents the Holy Grail of modern medicine.

The ability to edit genes at the germline level brings immense prospects for human health and welfare. Clinical applications that have only ever existed in science fiction are now within the realm of reality. Scientists have developed basic tools that may soon be used to prevent a myriad of debilitating and fatal genetic diseases including Cystic Fibrosis, Tay-Sachs, certain types of cancer, and hereditary forms of Parkinson's Disease, Amyotrophic Lateral Sclerosis (ALS), and Alzheimer's Disease.

Despite the vast potential for good, gene editing for clinical purposes is controversial. Jennifer Doudna, a gene editing pioneer, stated she is "uncomfortable" with the clinical applications of the technology. She and others have previously argued for a moratorium on germline editing citing unknown risks, safety, and efficacy concerns.

However, the latest germline editing report suggests that many of the concerns against future use of gene editing technologies for gene repair in human embryos may be premature and overstated. The study sought to correct a mutated version of the MYBPC3 gene, which causes hypertrophic cardiomyopathy, a heritable disease that leads to sudden cardiac failure, often in young athletes.

The study revealed that co-injecting the CRISPRCas9 system and sperm carrying the faulty MYBPC3 into healthy donor eggs corrected the pathogenic mutation. Importantly, the researchers overcame many of the problems associated with editing of human embryos that Chinese teams have experienced since 2015.

By injecting the gene editing system before the first cell division, the researchers discovered that mosaicism a characteristic of embryos that have a mix of edited and unedited cells could be avoided. This strategy led to highly precise and accurate editing, as evidenced by the lack of unintended off-target mutations in the embryos' genomes.

Progress aside, germline editing is not yet ready for primetime. Further research and considerable technology optimization are essential prerequisites for clinical use. Laws that prohibit clinical trials may be reconsidered, in due course, as the technology develops. That all takes time.

Researchers know this. Unfortunately, scientific progress is frequently susceptible to sensationalism.

Unjustified debates concerning germline editing often conjure up eugenics. Alluring and frivolous claims that reproductive technologies will inevitably be used to create tall, beautiful, superhuman geniuses with superb athletic abilities circulate ad nauseam. The myth of "designer babies" has become an emblem of misinformation.

Never mind that the quest to uncover specific intelligence gene(s) has proven to be an exercise in futility. Research shows that, while heritable, highly polygenic traits those determined by multiple genesare often determined by the collective contribution of hundreds of genes. For instance, hundreds of genetic variants in at least 180 genetic loci have been reported to influence height in humans.

Knowledge concerning the genetics of complex polygenic traits is vastly incomplete. The notion that scientists can tinker with a few genes let alone hundreds of them simultaneously, and know precisely how such manipulation will affect an individual is simply preposterous at this time. And it will likely remain so during our lifetimes.

That scientific fact favors gradual and thoughtful measures including legislation and policymakingto address actual concerns raised by germline editing. Entertaining dubious hypotheticals is a dangerous endeavor. And seeking to ban a technology over far-fetched contingencies is bad policy.

So be skeptical when encountering views that aver humans are entering a Brave New World. Be skeptical when scientific progress is reduced to a Frankenstein-like fable engineered to pollute thoughtful debate. The designer baby canard must be confronted.

We are indeed entering a new exciting world. One in which human ingenuity can and will be used to eradicate disease and suffering by pushing the boundaries of knowledge.

We should all embrace this momentous time in human history.

Paul Enrquez is a lawyer and scientist. His work focuses on the intersection of science and law and has been featured in legal and scientific journals. He explores gene editing as it relates to eugenics and the genetics of human intelligence in his recently published article "Genome Editing and the Jurisprudence of Scientific Empiricism."

The views expressed by contributors are their own and not the views of The Hill.

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Why we should all embrace gene editing in human embryos - The Hill (blog)

Hospitals & Health Networks

Genomic Medicine Has Entered the Building Hospitals & Health Networks In July, the group published a report in the New England Journal of Medicine describing a variant of the gene ANGPTL3 associated with a reduced risk of cardiovascular disease detected in some MyCode participants. The gene variant codes for a protein ...

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Genomic Medicine Has Entered the Building - Hospitals & Health Networks

Jennifer Doudna, Ph.D. , professor, Molecular and Cell Biology and Chemistry, University of California, Berkeley. (UC-Berkeley)

Jennifer Doudna, Ph.D. , professor, Molecular and Cell Biology and Chemistry, University of California, Berkeley. (UC-Berkeley)

Luciano Marraffini, Ph.D., associate professor, Laboratory of Bacteriology, The Rockefeller University, New York City. (Mario Morgado)

Luciano Marraffini, Ph.D., associate professor, Laboratory of Bacteriology, The Rockefeller University, New York City. (Mario Morgado)

Gene-editing scientists to share $500K Albany Med prize

Albany

Five scientists whose work on the revolutionary gene-editing technology CRISPR will share the 2017 Albany Medical Center Prize in Medicine and Biomedical Research.

The decision by the Albany Prize National Selection Committee to award the $500,000 prize to these researchers stands out from recent announcements of the prestigious award, which have acknowledged scientists for groundbreaking work leading to current medical advances. While developments using CRISPR have exploded this year, its use in humans remains a promise, but one with far-reaching effects.

"The committee saw this technology as having huge potential for eradicating human disease," said Dr. Vincent Verdile, dean of Albany Medical College and chair of the prize committee.

CRISPR (pronounced "crisper") stands for "clustered regularly interspaced short palindromic repeats." It is a DNA sequence that simple bacteria use to defend themselves against viruses by snipping out part of the virus DNA so it can be recognized by the bacteria's own immune systems. The technology based on it lets scientists "edit" genes at specific locations by removing, adding or altering parts of the DNA sequence.

In the last year, CRISPR technology has been used to remove a gene linked to heart disease from human embryos and to create a cancer-killing gene that shrinks tumors in mice. Last week, scientists revealed in the journal Science that they had created piglets stripped of viruses that could cause disease in humans; the technique could open the door for eventual transplantation of livers, hearts and other organs from pigs to people.

The scientists who will share the Albany Prize are:

Emmanuelle Charpentier of the Max Planck Institute for Infection Biology in Germany. Charpentier is co-inventor and co-owner of the intellectual property comprising the CRISPR gene-editing system, and co-founder of two companies developing the technology for biotech and biomedical applications.

Jennifer Doudna of the University of California, Berkeley. Five years ago, Doudna described a simple way of editing the DNA of any organism using an RNA-guided protein founded in bacteria.

Luciano Marraffini of Rockefeller University in New York City. Marraffini discovered that CRISPR works by severing DNA and was the first to propose that it could be used to edit genes in organisms other than bacteria. With Feng Zhang, he performed the first successful CRISPR gene-editing experiment in human cells.

Francisco J.M. Mojica of the University of Alicante in Spain. Mojica's work has led to the development of tools used in the genetic manipulation of any living being, including humans.

Feng Zhang of the Broad Institute of Massachusetts Institute of Technology and Harvard University. Zhang pioneered the development of gene editing tools for use in human cells from bacterial CRISPR systems.

The Albany Prize Committee's selection of five scientists to share the award this year reflects an increasing trend in science toward collaboration, where information is shared and groups of researchers move knowledge forward in ways that no one of them could do alone, Verdile said. It's a major change since the days when a single scientist would be credited with, say, the discovery of a vaccine.

"That's more of where the future of biomedical research is going what's good for the good of mankind, not me personally," Verdile said.

News reports in recent years have focused on the ethical aspects of CRISPR technology, which in addition to its potential to prevent devastating diseases, could also be used for cosmetic purposes or have unintended consequences that affect the descendants of the person whose genes are edited. The Albany Prize Committee did not consider such "what if" scenarios, Verdile said, leaving those conversations for future ethicists and policymakers as specific medical techniques are developed.

The Albany Prize, one of the nation's largest for science and medicine, was established in 2000 by the late Morris "Marty" Silverman, a New York City businessman and philanthropist who grew up in Troy. A commitment of $50 million from the Marty and Dorothy Silverman Foundation allows for the prize to be awarded annually for 100 years.

Albany Med released the 2017 award recipients' names Tuesday morning. The recipients will formally receive their awards at a Sept. 27 ceremony in Albany.

chughes@timesunion.com 518-454-5417 @hughesclaire

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Gene-editing scientists to share $500K Albany Med prize - Albany Times Union

By KIMBERLY HOUGHTON Union Leader Correspondent August 14. 2017 11:06PM

This sequence of images shows the development of embryos after being injected with a biological kit to edit their DNA, removing a genetic mutation known to cause hypertrophic cardiomyopathy.(Oregon Health & Science University)

Bryan Luikart, an associate professor of molecular and systems biology at Geisel School of Medicine at Dartmouth College.

It is pretty amazing. It is a super-exciting time to be a scientist right now, said Bryan Luikart, an associate professor of molecular and systems biology at Geisel School of Medicine at Dartmouth College.

The study, which was published in the journal Nature, was detailed in a New York Times report. According to the article, Oregon researchers reported they repaired dozens of human embryos, fixing a mutation that causes a common heart condition that can lead to sudden death later in life.

The way they have dodged some ethical considerations is that they didnt go on to have that embryo grow into a person, said Luikart, explaining that if the embryos with the repaired mutation did have the opportunity to develop, they would be free of the heart condition.

At the Geisel School of Medicine at Dartmouth, Luikart and his colleagues have already been using this concept with mouse embryos, focusing specifically on autism.

Researchers are using the gene-editing method called CRISPR-Cas9 in hopes of trying to more fully understand autism, which he said is the most critical step in eventually finding a cure.

I think the CRISPR is a tremendous breakthrough. The question really is where and when do you want to use it, Luikart said. I have no ethical concerns using it as a tool to better understand biology.

The new milestone, an example of human genetic engineering, does carry ethical concerns that Luikart said will trigger some debates. He acknowledged that while the advancement of gene-editing technology could eventually stop unwanted hereditary conditions, it also allows for creating babies with smarter, stronger or more attractive traits.

The ability to do that is now within our grasp more than it has ever been, he said.

More importantly, the breakthrough could ultimately eliminate diseases, Luikart said. As the technology advances, he said, genetic diseases that are passed down to children may be corrected before the child receives them.

He used another example of a brain tumor, which often returns after it is surgically removed. Now, once the brain tumor is removed, there is the possibility of placing something in the space to edit and fix the mutation that causes the brain tumor in the first place if physicians are able to find the right cell to edit, Luikart said.

People are definitely thinking along those lines, or cutting the HIV genome, said Luikart, who predicts that those advancements will occur in mice within the next decade, and the ability to do that in humans is definitely there.

The big question is whether that can occur without some sort of side effect that was not predicted, he said.

Columbia University Medical Center posted an article earlier this year warning that CRISPR gene editing can cause hundreds of unintended mutations, based on a study published recently in Nature Methods.

This past May, MilliporeSigma announced it has developed a new genome editing tool that makes CRISPR more efficient, flexible and specific, giving researchers more experimental options and faster results that can accelerate drug development and access to new therapies, according to a release.

CRISPR genome editing technology is advancing treatment options for some of the toughest medical conditions faced today, including chronic illnesses and cancers for which there are limited or no treatment options, states the release, adding the applications of CRISPR are far ranging from identifying genes associated with cancer to reversing mutations that cause blindness.

It is pretty big news, Luikart said.

khoughton@newstote.com

Health Hanover

Original post:
New Hampshire biologist reacts to gene-editing discovery - The Union Leader

In BriefResearchers from UC San Diego's School of Medicine have testeda modified CRISPR-Cas9 technique designed to target RNA instead ofDNA. Rcas9 could potentially improve the lives of patients withALS, Huntington's disease, or myotonic dystrophy by delaying theprogression of their disorders. Editing RNA

The most efficient and effective gene-editing tool in use today is CRISPR-Cas9. Just this year, researchers have successfully used it fora wide variety of experiments, from modifying garden vegetables to encoding a GIF in bacterial DNA. Most recently, the tool was used to remove a genetic disease from a human embryo.

Although undeniably powerful, CRISPR-Cas9 does have its limitations; it can only target DNA. To extend its capabilities to includeRNA editing, researchers from the University of California San Diego (UCSD) School of Medicinedeveloped amodification of CRISPR, and theyre calling their toolRNA-targeting Cas9 (RCas9).

In a study published in Cell, the UCSD team tested their technique by correcting the kinds of molecular mistakes that cause people to develop microsatellite repeat expansion diseases, such ashereditary amyotrophic lateral sclerosis (ALS)and Huntingtons disease.

During standard CRISPR-CAs9 gene editing, a guide RNA is instructed to deliver a Cas9 enzyme to a specific DNA molecule. The researchers from UCSD instead instructed it to target an RNA molecule.

Tests conducted in the laboratory showed that RCas9 removed 95 percent ofproblem-causing RNA for myotonic dystrophy types 1 and 2, Huntingtons disease, and one type of ALS. The technique also reversed 93 percent of the dysfunctional RNA targets in the muscle cells of patients with myotonic dystrophy type 1, resulting in healthier cells.

This is exciting because were not only targeting the root cause of diseases for which there are no current therapies to delay progression, but weve re-engineered the CRISPR-Cas9 system in a way thats feasible to deliver it to specific tissues via a viral vector, senior author Gene Yeo, a cellular and molecular medicine professor at UCSD School of Medicine, explained in a press release.

Across the globe, an estimated 450,000 patients are said to be living with ALS. Roughly 30,000 of those are from the U.S. where 5,600 people are diagnosed with the diseases every year. The exact number of Huntingtons disease cases, however, isnt quite as easy to pin down. One estimate says that around 30,000 Americans display symptoms of it, while more than 200,000 are at risk.

Regardless of the exact numbers, these two neurological diseases clearly affect a significant number of people. This prevalence and the absence of a known curemakes the UCSD teams research all the more relevant. Even more exciting is the fact that the same kinds of RNA mutations targeted by this study are known to cause more than 20 other genetic diseases.

Our ability to program the RCas9 system to target different repeats, combined with low risk of off-target effects, is its major strength, co-first author of the study Ranjan Batra said in the UCSD press release.

However, the researchers do know that what theyve accomplished is just a first step. While RCas9 works in a lab, they still have to figure out how it will fare when tested in actual patients.

The main thing we dont know yet is whether or not the viral vectors that deliver RCas9 to cells would elicit an immune response, explained Yeo. Before this could be tested in humans, we would need to test it in animal models, determine potential toxicities, and evaluate long-term exposure.

Ultimately, while RCas9 couldnt exactly deliver a cure, it could potentially extend patients healthy years. For disease like ALS and Huntingtons, thats a good place to start.

Read more:
A New Gene Editing Technique Could Finally Allow Us to Treat ALS - Futurism