Category Archives: Gene Medicine

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A leading genome-editing researcher is urging extra caution as drug companies race to turn the landmark technology he helped create into human medicine.

In a paper published today in Nature Medicine, Feng Zhang of the Broad Institute of MIT and Harvard and colleague David Scott argue that researchers should analyze the DNA of patients before giving them experimental medicines that alter their genes with the breakthrough technology CRISPR. The suggestion, among others in the paper, stems from a deeper look at the wide array of subtle differences in human DNA.

Zhang is a key inventor of CRISPR-Cas9, which describes a two-part biological system that slips into the nucleus of cells and irreversibly alters DNA. One part is an enzyme, natures molecular scissors, which cuts DNA. The second part is a string of ribonucleic acid (RNA) that guides the enzyme to the proper spot. In five years since its invention, CRISPR-Cas9 has become a mainstay of biological research, and researchers including Zhang (pictured above) have moved quickly to improve upon its components. His work is at the center of a long-running patent battle to determine ownership of the technology.

Zhang and Scotts recommendation taps into a long-running debate in the gene-editing field about off-target effectsthe fear of misplaced cuts causing unintended harm. Most recently, the FDA took up a similar issue at a meeting to assess a type of cell therapy, known as CAR-T, for kids with leukemia. The FDA highlighted the risk that the cells, which have certain genes edited to make them better cancer fighters, may cause secondary cancers long after a patients leukemia has been cured. (FDA advisors unanimously endorsed the therapys approval nonetheless.)

Some researchers say there should be near certainty that gene altering techniques wont go awry before testing in humans, caution that stems in part from gene therapy experiments in the U.S. and Europe nearly 20 years ago that killed an American teenager and triggered leukemia in several European boys.

While no medicine is risk-free, other researchers say the tools to gauge risk have improved.

Andy May, senior director of genome engineering at the Chan Zuckerberg Biohub in San Francisco, calls Zhang and Scotts recommendation for patient prescreening a good discussion point, but the danger is someone will pick up on this and say you cant push forward [with a CRISPR drug] until everyone is sequenced.

Its an extremely conservative path to take, says May, who until recently was the chief scientific officer at Caribou Biosciences, a Berkeley, CA-based firm in charge of turning the discoveries of UC Berkeleys Jennifer Doudna and her colleagues into commercial technology. (May was also a board member of Cambridge, MA-based Intellia Therapeutics (NASDAQ: NTLA), which has exclusive license to use Caribous technology in human therapeutics.)

Berkeley is leading the challenge to Zhangs CRISPR patents and last week filed the first details in its appeal of a recent court decision in favor of Zhang and the Broad Institute.

Zhang sees prescreening as a form of companion diagnostic, which drug companies frequently use to identify the right patients for a study. A whole genome sequencewhich costs about $1,000could filter out patients unlikely to benefit from a treatment or at higher risk of unintended consequences, such as cancer. In the long run, it could also encourage developers to create more variations of a treatment to make genome-editing based therapeutics as broadly available as possible, said Zhang.

Its well known that human genetic variation is a hurdle in the quest to treat genetic diseases either by knocking out disease-causing genes or replacing them with healthy versions. But Zhang and Scott use newly available genetic information to deepen that understanding. In one Broad Institute database with genetic information from more than 60,000 people, they find one genetic variation for every eight letters, or nucleotides, in the exomethat is, the sections of DNA that contain instructions to make proteins. (There are 6 billion nucleotides in each of our cells.) The wide menu of differences is, in effect, an open door to misplaced cuts that CRISPRs enzymes might be prone to.

Zhang and others are working on many kinds of enzymes, from variations on the workhorse Cas9, to new ones entirely. He and Scott found that the deep pool of genetic variation makes some forms of the Cas enzyme more likely than others to go awry, depending on the three-nucleotide sequence they lock onto in the targeted DNA.

Zhang and Scott write that CRISPR drug developers should avoid trying to edit DNA strings that are likely to have high variation. In their paper, they examine 12 disease-causing genes. While more common diseases, such as those related to high cholesterol, will contain higher genetic variation because of the broader affected population, every gene, common or not, contains regions of high and low variation. Zhang and Scott say developers can build strategies around the gene regions they are targeting.

For example, going after a more common disease might require a wider variety of product candidates, akin to a plumber bringing an extra-large set of wrenches, with finer gradations between each wrench, to a job site with an unpredictable range of pipe sizes.

CRISPR companies say they are doing just that. We have always made specificity a fundamental part of our program, says Editas Medicine CEO Katrine Bosley. Zhang is a founder of Editas (NASDAQ: EDIT), which has exclusive license to the Broads Next Page

Alex Lash is Xconomy's National Biotech Editor. He is based in San Francisco.

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CRISPR Pioneer Zhang Preaches Extra Caution In Human Gene Editing - Xconomy

For the first time in the United States, scientists have edited the genes of human embryos, a controversial step toward someday helping babies avoid inherited diseases.

The experiment was just an exercise in science the embryos were not allowed to develop for more than a few days and were never intended to be implanted into a womb, according to MIT Technology Review, which first reported the news.

Officials at Oregon Health & Science University confirmed Thursday that the work took place there and said results would be published in a journal soon. It is thought to be the first such work in the U.S.; previous experiments like this have been reported from China. How many embryos were created and edited in the experiments has not been revealed.

The Oregon scientists reportedly used a technique called CRISPR, which allows specific sections of DNA to be altered or replaced. It's like using a molecular scissors to cut and paste DNA, and is much more precise than some types of gene therapy that cannot ensure that desired changes will take place exactly where and as intended. With gene editing, these so-called "germline" changes are permanent and would be passed down to any offspring.

The approach holds great potential to avoid many genetic diseases, but has raised fears of "designer babies" if done for less lofty reasons, such as producing desirable traits.

Last year, Britain said some of its scientists could edit embryo genes to better understand human development.

And earlier this year in the U.S., the National Academy of Sciences and National Academy of Medicine said in a report that altering the genes of embryos might be OK if done under strict criteria and aimed at preventing serious disease.

"This is the kind of research that the report discussed," University of Wisconsin-Madison bioethicist R. Alta Charo said of the news of Oregon's work. She co-led the National Academies panel but was not commenting on its behalf Thursday.

"This was purely laboratory-based work that is incredibly valuable for helping us understand how one might make these germline changes in a way that is precise and safe. But it's only a first step," she said.

"We still have regulatory barriers in the United States to ever trying this to achieve a pregnancy. The public has plenty of time" to weigh in on whether that should occur, she said. "Any such experiment aimed at a pregnancy would need FDA approval, and the agency is currently not allowed to even consider such a request" because of limits set by Congress.

One prominent genetics expert, Dr. Eric Topol, director of the Scripps Translational Science Institute in La Jolla, Calif., said gene editing of embryos is "an unstoppable, inevitable science, and this is more proof it can be done."

Experiments are in the works now in the U.S. using gene-edited cells to try to treat people with various diseases, but "in order to really have a cure, you want to get this at the embryo stage," he said. "If it isn't done in this country, it will be done elsewhere."

There are other ways that some parents who know they carry a problem gene can avoid passing it to their children, he added. They can create embryos through in vitro fertilization, screen them in the lab and implant only ones free of the defect.

Dr. Robert C. Green, a medical geneticist at Harvard Medical School, said the prospect of editing embryos to avoid disease "is inevitable and exciting," and that "with proper controls in place, it's going to lead to huge advances in human health."

The need for it is clear, he added: "Our research has suggested that there are far more disease-associated mutations in the general public than was previously suspected."

Hank Greely, director of Stanford University's Center for Law and the Biosciences, called CRISPR "the most exciting thing I've seen in biology in the 25 years I've been watching it," with tremendous possibilities to aid human health.

"Everybody should calm down" because this is just one of many steps advancing the science, and there are regulatory safeguards already in place. "We've got time to do it carefully," he said.

Michael Watson, executive director of the American College of Medical Genetics and Genomics, said the college thinks that any work aimed at pregnancy is premature, but the lab work is a necessary first step.

"That's the only way we're going to learn" if it's safe or feasible, he said.

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In US first, scientists edit genes of human embryos - Indiana Gazette

Sun., July 30, 2017, 8:58 p.m.

Dr. Mary Kay Lobo and her colleagues at the University of Maryland School of Medicine have been examining the gene known as Slc6a15 and researching the role it plays in either protecting from stress or contributing to depression. (Karl Merton Ferron / Karl Merton Ferron/Baltimore Sun)

BALTIMORE Although there are medications to treat depression, many scientists arent sure why theyre effective and why they dont work for everyone.

Researchers at the University of Maryland School of Medicine believe they may have found a key to the puzzle of major depression that could lead to therapies for those who dont respond to medications already on the market.

A study by the researchers has identified the central role a gene known as Slc6a15 plays in either protecting from stress or contributing to depression, depending on its level of activity in a part of the brain associated with motivation, pleasure and reward seeking.

Published in the Journal of Neuroscience in July, the study is the first to illuminate in detail how the gene works in a kind of neuron that plays a key role in depression, the according to the medical school.

Specifically, the researchers found that mice with depression had reduced levels of the genes activity, while those with high levels of the genes activity handled chronic stress better.

Though senior researcher Mary Kay Lobos primary studies were done with mice, she also examined the brains of people who had committed suicide and found reduced levels of the genes activity, confirming a likely link.

She hopes now that drugs could be developed that would encourage the genes activity.

I thought it was fascinating we had this system in place that allows us to go after things or be motivated or have pleasure and I was interested in how it becomes dysfunctional in certain diseases like depression, Lobo said. I hope that we can identify molecules that could potentially be therapeutically treated or targeted to treat depression.

Lobo and her colleagues have been examining the gene for years. In 2006, they discovered that it was more common among specific neurons in the brain that they later learned were related to depression. Five years later, other researchers learned that the gene played a role in depression and Lobo and her research colleagues decided to investigate what that role is in those specific neurons.

About 15 million adults, or 6.7 percent of all U.S. adults, experience major depression in a given year, according to the Anxiety and Depression Association of America. It is the leading cause of disability for Americans ages 15 to 44. It is more prevalent in women and can develop at any age, but the median age of onset is 32.5.

David Dietz, an associate professor in the Department of Pharmacology and Toxicology at the State University of New York at Buffalo, said little was known previously about the biological basis of depression in the brain. Many drugs used to treat depression were discovered serendipitously, he said, and it wasnt clear why they worked.

Were starting to really get an idea of what does the depressed brain look like, Dietz said. When you put the whole puzzle together, you see where the problem is. For too long weve been throwing things at individual pieces. Its so complex and we have so little information that it was almost bound to be that way. For the first time this is one of those bigger pieces you can slide into the jigsaw puzzle.

Lobo said its not clear yet how Slc6a15 works in the brain, but she believes it may be transporting three types of amino acids into a subset of neurons called D2 neurons in a part of the brain called the nucleus accumbens. The nucleus accumbens and D2 neurons are known to play a role in pleasure, activating when one eats a delicious meal, has sex or drinks alcohol.

The amino acids would then be synthesized into neurotransmitters. Depression previously has been linked to imbalances of the neurotransmitters serotonin, norepinephrine and dopamine.

So even though people may have proper levels of amino acids in their bodies, the neurons in their brains that need them may not be getting enough if the transporter is not working as it should.

This gene is critical for putting very specific amino acids in the right place so that neurotransmitters can be synthesized, said A.J. Robison, an assistant professor in the Department of Physiology at Michigan State University. Its the location, location, location idea. Its not the amino acids, its where theyre at and in which cells.

Robison said Lobos next step would be discovering more about how the transporter gene works.

The fact that this transporter seems to be important is what the paper shows and how it does it is not shown, and thats a challenge for her, he said. Figuring out the how of it is the next step and Dr. Lobo is particularly positioned to do it.

Lobos team was able to use gene therapy, a form of therapy in the early stages of being studied in humans, in the mice to boost the genes activity. The mice were exposed to larger, more aggressive mice, which usually causes depressive symptoms. But the gene therapy helped protect the mice against the stress, the team found. When the team reduced the genes activity in the mice, just one day of exposure to the aggressive mice was enough to cause symptoms of depression.

Gene therapy is starting to be used in the treatment of some types of cancers, but Lobo said science had not yet advanced to the point where it can be used for treating neurological issues in human patients. A more likely treatment would be a drug that targets the genes activity directly, she said.

I think this is a major step toward our understanding of the precise maladaptive changes that occur in response to stress, said Vanna Zachariou, an associate professor in the Department of Neuroscience at the Icahn School of Medicine at Mount Sinai. It can be a more efficient way to target depression because its not simply targeting monoamine receptors or dopamine but targeting molecular adaptations that occur. It doesnt act necessarily as the drugs we have available, so it might create an alternative avenue to treat depression.

Lobo said she wouldnt refer to Slc6a15 as a depression gene, saying the disease was complex and could have many factors.

I wouldnt say theres one depression gene she said. A number of things play a role, and also theres no depression neuron, theres multiple depression neurons.

There also may be different types of depression with different symptoms, she said. With the disease, some sufferers sleep a lot, while others sleep a lot less, for example.

With all these complex diseases, its hard to link it to something, she said. Like Huntingtons disease, we know theres a specific gene that causes Huntingtons disease. For depression we dont have that.

Read the rest here:
Maryland scientists research gene linked to depression | The ... - The Spokesman-Review

Publishing in the July 24, 2017, issue of Nature Communications, Professor Klaus Ley, M.D., who led the study, and his team identify gene markers that directly correlate with the outcome of inflammatory and malignant diseases in humans, including survival of osteosarcoma, melanoma, chronic lymphocytic leukemia (CLL), Burkitt lymphoma and large-cell lung carcinoma. Their findings emphasize that accounting for immune diversity is a critical factor to increase the success rate of predicting disease outcomes based on immune cell measurements.

Traditionally, researchers have relied on inbred mouse strains to gain insight into the complex world of human diseases while reducing what is known as experimental noise. If you take a black, a brown or a white mouse each one will give you a different answer in the same assay. For example, if you vaccinate them, their responses will be different, which creates a lot of experimental noise, says Ley. However, when you think about patients, or even healthy people, we are all different.

To mine those differences for valuable information, the LJI researchers actively embraced the experimental noise. Instead of analyzing a single inbred mouse strain, Buscher turned to the hybrid mouse diversity panel (HDMP). The panel was developed by co-author Aldons J. Lusis, Ph.D., a professor in the Departments of Medicine, Human Genetics, and Microbiology, Immunology, and Molecular Genetics at the University of California, Los Angeles.

The HDMP is a panel of about 100 different inbred mouse strains that mirror the breadth of genetic and immunological diversity found in the human population. You can think of the panel as a hundred different patients, or healthy people, explain Buscher.

Buscher, Lusis, Ley and others studied the natural variation in the activation pattern of abdominal macrophages, versatile members of the immune system. Professional phagocytes, they clear worn-out cells and cellular debris; survey tissue surfaces for foreign invaders; engulf bacteria and cancer cells; increase or quiet down inflammation and recruit other members of the immune system.

Macrophages isolated from 83 different mouse strains from the HDMP were exposed to lipopolysaccharide (LPS), a major component of the outer wall of gram-negative bacteria, to gauge their reaction to the strong inflammatory. Gram-negative bacteria are the cause of wide range of different illnesses, including food poisoning, cholera, tuberculosis and periodontitis, among many others.

Fundamentally, when the immune system is confronted with gram-negative bacteria, it can deal with the situation in two ways: Either, it gets very angry and tries to kill the bacteria or it can wall them off in an attempt to live with it, explains Ley. Both strategies carry a certain risk but a long evolutionary history has insured that mice and people can survive with either strategy.

The LPS-induced reactions of the macrophages analyzed as part of the study covered the whole spectrum from very aggressive (LPS+) to very tolerant (LPS-) depending on the mouse strain. This LPS+ and LPS- designation is related to the M1 and M2 designation introduced by Charles D. Mills, another co-author of the study. Next, the researchers asked which genes were active during each response type to identify gene signatures that correlated with LPS-responsiveness. Ley and his team then ran these gene signatures across various human gene expression data sets and discovered that they strongly correlated with human disease outcomes.

For example, macrophages isolated from healthy joints were enriched in LPS-tolerant genes, whereas macrophages from rheumatoid arthritis patients were strongly skewed towards LPS-aggressive. The same held true for macrophages found in the kidneys of healthy people versus lupus erythematosus patients.

Since it had been known that mice and people with the aggressive phenotype are better at fighting canceralthough they are more susceptible to cardiovascular diseasethe scientists specifically asked whether the level of LPS-responsiveness could predict tumor survival.

After analyzing data from 18,000 biopsies across 39 different tumor types, they found that the LPS+ gene signature strongly correlated with survival while the LPS- signature correlated with cancer death. The pattern was significant across many different types of cancer, including osteosarcoma, melanoma, chronic lymphocytic leukemia, Burkitt lymphoma and large-cell lung carcinoma.

This article has been republished frommaterialsprovided byLa Jolla Institute for Allergy and Immunology. Note: material may have been edited for length and content. For further information, please contact the cited source.

Excerpt from:
Gene Markers Can Predict Your Outcome of Cancer or Immune Disease - Technology Networks

Although medications exist to treat depression, many scientists arent sure why theyre effective and why they dont work for everyone.

Researchers at the University of Maryland School of Medicine believe they may have found a key to the puzzle of major depression that could lead to therapies for those who dont respond to medications already on the market.

A new study by the researchers has identified the central role a gene known as Slc6a15 plays in either protecting from stress or contributing to depression, depending on its level of activity in a part of the brain associated with motivation, pleasure and reward seeking.

Published in the Journal of Neuroscience in July, the study is the first to illuminate in detail how the gene works in a kind of neuron that plays a key role in depression, according to the University of Maryland School of Medicine.

Specifically, the researchers found that mice with depression had reduced levels of the genes activity, while those with high levels of the genes activity handled chronic stress better.

Though senior researcher Mary Kay Lobos primary studies were done with mice, she also examined the brains of people who had committed suicide and found reduced levels of the genes activity, confirming a likely link.

She hopes now that drugs could be developed that would encourage the genes activity.

I thought it was fascinating we had this system in place that allows us to go after things or be motivated or have pleasure and I was interested in how it becomes dysfunctional in certain diseases like depression, Lobo said. I hope that we can identify molecules that could potentially be therapeutically treated or targeted to treat depression.

Lobo and her colleagues have been examining the gene for years. In 2006, they discovered that it was more common among specific neurons in the brain that they later learned were related to depression. Five years later, other researchers learned the gene played a role in depression and Lobo and her research colleagues decided to investigate what that role is in those specific neurons.

About 15 million adults, or 6.7 percent of all U.S. adults, experience major depression in a given year, according to the Anxiety and Depression Association of America. It is the leading cause of disability for Americans aged 15 to 44. It is more prevalent in women and can develop at any age, but the median age of onset is 32.5.

David Dietz, an associate professor in the Department of Pharmacology and Toxicology at the State University of New York at Buffalo, said little was known previously about the biological basis of depression in the brain. Many drugs used to treat depression were discovered serendipitously, he said, and it wasnt clear why they worked.

Were starting to really get an idea of what does the depressed brain look like, Dietz said. When you put the whole puzzle together, you see where the problem is. For too long weve been throwing things at individual pieces. Its so complex and we have so little information that it was almost bound to be that way. For the first time this is one of those bigger pieces you can slide into the jigsaw puzzle.

Lobo said its not clear yet how Slc6a15 works in the brain, but she believes it may be transporting three types of amino acids into a subset of neurons called D2 neurons in a part of the brain called the nucleus accumbens. The nucleus accumbens and D2 neurons are known to play a role in pleasure, activating when one eats a delicious meal, has sex or drinks alcohol.

The amino acids would then be synthesized into neurotransmitters. Depression previously has been linked to imbalances of the neurotransmitters serotonin, norepinephrine and dopamine.

So even though people may have proper levels of amino acids in their bodies, the neurons in their brains that need them may not be getting enough if the transporter is not working as it should.

This gene is critical for putting very specific amino acids in the right place so that neurotransmitters can be synthesized, said A.J. Robison, an assistant professor in the Department of Physiology at Michigan State University. Its the location, location, location idea. Its not the amino acids, its where theyre at and in which cells.

Robison said Lobos next step would be discovering more about how the transporter gene works.

The fact that this transporter seems to be important is what the paper shows and how it does it is not shown, and thats a challenge for her, he said. Figuring out the how of it is the next step and Dr. Lobo is particularly positioned to do it.

Lobos team was able to use gene therapy, a form of therapy in the early stages of being studied in humans, in the mice to boost the genes activity. The mice were exposed to larger, more aggressive mice, which usually causes depressive symptoms. But the gene therapy helped protect the mice against the stress, the team found. When the team reduced the genes activity in the mice, just one day of exposure to the aggressive mice was enough to cause symptoms of depression.

Gene therapy is starting to be used in the treatment of some types of cancers, but Lobo said science had not yet advanced to the point where it can be used for treating neurological issues in human patients. A more likely treatment would be a drug that targets the genes activity directly, she said.

I think this is a major step toward our understanding of the precise maladaptive changes that occur in response to stress, said Vanna Zachariou, an associate professor in the Department of Neuroscience at the Icahn School of Medicine at Mount Sinai. It can be a more efficient way to target depression because its not simply targeting monoamine receptors or dopamine but targeting molecular adaptations that occur. It doesnt act necessarily as the drugs we have available, so it might create an alternative avenue to treat depression.

Lobo said she wouldnt refer to Slc6a15 as a depression gene, saying the disease was complex and could have many factors.

I wouldnt say theres one depression gene she said. A number of things play a role, and also theres no depression neuron, theres multiple depression neurons.

There also may be different types of depression with different symptoms, she said. With the disease, some sufferers sleep a lot, while others sleep a lot less, for example.

With all these complex diseases, its hard to link it to something, she said. Like Huntingtons disease, we know theres a specific gene that causes Huntingtons disease. For depression we dont have that.

cwells@baltsun.com

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University of Maryland scientists research gene linked to depression - Baltimore Sun

Technology that allows alteration of genes in a human embryo has been used for the first time in the United States, according to Oregon Health and Science University (OHSU) in Portland, which carried out the research.

The OHSU research is believed to have broken new ground both in the number of embryos experimented upon and by demonstrating it is possible to safely and efficiently correct defective genes that cause inherited diseases, according to Technology Review, which first reported the news.

None of the embryos were allowed to develop for more than a few days, according to the report.

Some countries have signed a convention prohibiting the practice on concerns it could be used to create so-called designer babies.

Results of the peer-reviewed study are expected to be published soon in a scientific journal, according to OHSU spokesman Eric Robinson.

The research, led by Shoukhrat Mitalipov, head of OHSU's Center for Embryonic Cell and Gene Therapy, involves a technology known as CRISPR that has opened up new frontiers in genetic medicine because of its ability to modify genes quickly and efficiently.

CRISPR works as a type of molecular scissors that can selectively trim away unwanted parts of the genome, and replace it with new stretches of DNA.

Scientists in China have published similar studies with mixed results.

In December 2015, scientists and ethicists at an international meeting held at the National Academy of Sciences (NAS) in Washington said it would be "irresponsible" to use gene editing technology in human embryos for therapeutic purposes, such as to correct genetic diseases, until safety and efficacy issues are resolved.

But earlier this year, NAS and the National Academy of Medicine said scientific advances make gene editing in human reproductive cells "a realistic possibility that deserves serious consideration.

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First Editing of Human Embryos Performed in United States - NBCNews.com

Good news for people suffering from genetic diseases and for those who could be helped with stem cell therapies. This week, Stanford announced the creation of the Center for Definitive and Curative Medicine, a new center that aims to bring life-changing advances to millions of patients.

The Center for Definitive and Curative Medicine is going to be a major force in theprecision healthrevolution, saidLloyd Minor, MD, dean of the School of Medicine, in a press release. Our hope is that stem cell and gene-based therapeutics will enable Stanford Medicine to not just manage illness but cure it decisively and keep people healthy over a lifetime.

The center plans to tap the rich vein of stem cell and gene therapy research underway at Stanford. These techniques pinpoint problems causing disease and introduce functional copies of genes or cells to replace malfunctioning ones. Its exciting work with the potential to make real changes in patient lives and Stanford with its deep strengths in research and clinical care is poised to lead.

The release explains:

Housed within theDepartment of Pediatrics, the new center will be directed by renowned clinician and scientistMaria Grazia Roncarolo, MD, the George D. Smith Professor in Stem Cell and Regenerative Medicine, and professor of pediatrics and of medicine.

It is a privilege to lead the center and to leverage my previous experience to build Stanfords preeminence in stem cell and gene therapies, said Roncarolo, who is also chief of pediatric stem cell transplantation and regenerative medicine, co-director of theBass Center for Childhood Cancer and Blood Diseasesand co-director of theStanford Institute for Stem Cell Biology and Regenerative Medicine. Stanford Medicines unique environment brings together scientific discovery, translational medicine and clinical treatment. We will accelerate Stanfords fundamental discoveries toward novel stem cell and gene therapies to transform the field and to bring cures to hundreds of diseases affecting millions of children worldwide.

Previously: Stanford scientists describe stem-cell and gene-therapy advances in scientific symposium Photo of Maria Grazia Roncarolo by Norbert von der Groeben

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Stanford Center for Definitive and Curative Medicine to tackle genetic diseases - Scope (blog)

Enough of blaming your environment every time you come down with an illness. Heres a new possibility: it could all be in your genes.

And proponents of genetic medicine are pushing the practice a notch higher in Nigeria.

The premise is that specific genes are responsible for specific conditions, and finding the right gene is the silver bullet.

Genetic disorder in medicine is not very well recognised, says Hyung Goo Kim, associate professor in neuroscience and regenerative medicine department at Augusta University, USA.

Hes part of a team expanding the scope of regenerative medicine through lectures at the National Hospital, Abuja.

Many people suffer disease but the [cause] is not recognised. The point is to find the disease gene for diagnosis and in the long run cure and treatment.

If we can identify the gene causing the disorder then we can understand the biology of the disorder more than before. That way we can intervene to try to cure and treat.

Regenerative medicine works by allowing body tissues to reprogramme themselves to act in different ways depending on what they are required to do or where they are placed.

For this, researchers use pluripotent cells, capable of becoming just about anything, and abundant in bone marrow.

Every disease in your body system can actually be tackled if we engineer the production of stem cells to fight that disease, says Prosper Igboeli, a professor at University of Nigeria and Augusta University.

The science of regeneration makes it possible to induce pluripotent stem cells.

Igboeli cautiously explains it is like taking skin and reorganising it to make any cell, even sperm.

I dont like to say things that are not correct. But we are having this new feeling that we can take your skin and make sperm out of it.

The bone marrow is a reserve of cells that can be re-engineered and configured through passage, injected into organs and organs respond to that particular disease state and revert back to normal.

The payoff is in having your body produce what you need for a cure instead of popping pills.

The range is anything from infertility and diabetes to spinal cord injuries and cancer.

Some endeavours have reached clinical stage, including experimental treatment for premature ovarian failure and polycystic ovarian syndrome.

National Hospital is building up its interest in stem cell research and looking at bone marrow transplantation as a possibility.

Health care research provides answers to questions lingering in the minds of health care providers in terms of diseases they are trying to manage, says Dr Jafar Momoh, chief medical director of the hospital.

The first world spends a lot of money on research and National Hospital is trying to collaborate with various [nongovernmental organisations] to deliver on the mandate for research.

We are looking at bone marrow transplantation. This is something the country needs for various diseases.

Research here will bring in funding from donor agencies interested in new research areas. Hence we need a robust research program. We have published papers but we want to take it to another level: molecular genetics, stem cell medicine and bone marrow transplantation, said Momoh.

Genetic medicine research is big in Egypt and Tunisia.

The effort now is to build a network of experts and a network to accumulate a database to help identify disease genes.

Read more:
Sorry, it's all in your genes - Daily Trust

A U.S. research team has reportedly edited the DNA of a human embryo just as a sperm fertilizes an egg, well before its eight-cell stage.

alxpin/iStockphoto

By Kelly ServickJul. 27, 2017 , 2:30 PM

Since Chinese researchers announced the first gene editing of a human embryo 2 years ago, many expected that similar work in the United States was inevitable. Last night, the MIT Technology Review broke the news that such experiments have happened. The research, led by embryologist Shoukhrat Mitalipov of Oregon Health and Science University in Portland, also reportedly sidestepped problems of incomplete and off-target editing that plagued previous attempts, though details could not be confirmed since the work is not yet published and Mitalipov has so far declined to comment.

If a peer-reviewed paper bears out the news story, Its one more step on the path to potential clinical application, says bioethicist Jeffrey Kahn of Johns Hopkins University in Baltimore, Maryland, who served on a committee convened by the U.S. National Academy of Sciences (NAS) and the National Academy of Medicine in Washington, D.C., to address gene editing. The panels report earlier this year concluded that a clinical trial involving embryo editing would be ethically allowable under narrow circumstances.

The first published human embryoediting work, in 2015, used nonviable embryos and targeted a gene mutated in the heritable blood disorder beta thalassemia. But it revealed major shortcomings in applying the increasingly popular CRISPR gene-editing technology. The few embryos that took up the change made by CRISPR were a patchwork of edited and unchanged cells, and they bore unintended edits outside the targeted gene.

Another Chinese team, from Guangzhou Medical University, in March became the first to report repairing disease-causing mutations in viable embryos, but some still contained a patchy mix of edited cellsa phenomenon called mosaicism. In none of the Chinese efforts did the researchers go on to implant the manipulated embryos in women.

Sources familiar with the new work from Mitalipovs group told the MIT Technology Review that they had produced tens of successfully edited embryos, and had avoided the issue of mosaicism by injecting eggs with CRISPR right as they were fertilized with donor sperm. The Guangzhou team injected its CRISPR system into single-celled human embryosits not yet clear how much their timing differed from Mitalipovs. (The new research presumably relied on nonfederal government funding, since Congress prohibits the use of taxpayer funds on research that destroys human embryos.)

Concerns about mosaicism and off-target effects after the published work by the Chinese teams led some to conclude that CRISPR wasnt safe as a strategy for preventing a disease in a baby, much less adding some enhancement. But even with the apparent advance by the Oregon team, a U.S. clinical trial probably isnt imminent. Its noteworthy that theyve been able to make some of these claims, offers Michael Werner, executive director of the Alliance for Regenerative Medicine in Washington, D.C., who argued in a 2015 Nature commentary that ethical and safety issues should put germline editing research off limits. Its still a little premature to say that weve resolved all these safety issues now.

The NAS report notes that many inherited diseases can be prevented by selecting healthy embryos for in vitro fertilization, and that embryo editing might only be justified if it presents the only option for a couple to have a healthy biological child. Congress has meanwhile prohibited the U.S. Food and Drug Administration from reviewing applications for clinical trials involving embryo editing.

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First US team to gene-edit human embryos revealed - Science Magazine

The genome-editing tool CRISPR has been put to good use so far for such things as creating monkeys with targeted mutations and engineering Malaria-proof mutant mosquitoes. But bring anything human under the purview of gene-editing and youre staring at an altogether different beast.

Will this beast editing genes in human embryos be friendly or hostile? That has been the critical question facing scientists and policy makers in the field. But even as the debate rages on, a report of creating genetically modified human embryos using CRISPR technology in the United States has now emerged.

According to MIT Technology Review, Shoukhrat Mitalipov and his team at Oregon Health and Science University have fertilised human eggs with sperm known to carry inherited disease-related mutations. These mutations were then corrected using CRISPR and the embryo was allowed to develop over the next few days. Importantly, it was not implanted. (If not implanted, embryos dont develop into babies.) Results reportedly displayed successful modifications for the large part with few errors in editing.

This exercise is only the second instance of gene-editing in human embryos anywhere; the first such case was reported in China.

CRISPR, or clustered regularly interspaced short palindromic repeats, allows for modification of DNA sequences and gene function. The technology, which is a natural defence mechanism of bacteria, promises to correct genetic defects with excellent efficiency and precision.

Gene-editing, however, raises important ethical questions as even small errors could possibly lead to permanent problems in the human gene pool.

In February this year, an American science policy group instituted by the National Academy of Sciences and National Academy of Medicine okayed gene-editing in human embryos so long as it was used to prevent babies from being born with diseases or disabilities and when there was no reasonable alternative.

There was no clarity on the nature of the procedure how safe was it? or which exact genetic modifications were pursued by Mitalipov and team. This lack of transparency, as Wired has pointed out, doesnt help quell concerns about the exercise. It now remains to be seen what the next step is and how far we are from engineering disease-free humans.

Also Read: Genome Editing: The Benefits And The Ethics

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US Scientists Modify Genes In Human Embryos Using CRISPR - Swarajya