Saturday, August 5, 2017
Friday, August 4, 2017
U.S. Scientists Use CRISPR to Fix Genetic Disease in Human Embryos For the First Time
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This article originally appeared on Time.com.
Scientists have successfully used CRISPR, a tool that cuts DNA with more precision than any other genome editing technology, to fix a genetic defect in human embryos that can cause serious heart problems, according to a landmark new study in the journal Nature. This is the first use of CRISPR on human embryos in the U.S.
Chinese scientists have reported using CRISPR to correct genetic defects in human embryos, but some of the embryos they used weren’t viable.
Shoukhrat Mitalipov, from Oregon Health & Science University, collaborated with researchers at the Salk Institute, as well as with scientists from China and South Korea, to improve on those results. They applied CRISPR at the earliest stage possible—when the embryo is still a single cell—to ensure that the genetic changes they introduced were propagated to every cell of the embryo as it divided and developed. Because the embryos were created for research purposes only, none were allowed to develop beyond three days.
MORE: First CRISPR Human Trial Approved in the U.S.
CRISPR, which was introduced in 2012, precisely cuts DNA but does not repair it. If combined with other techniques, however, researchers say it could both cut out disease-causing genes and replace them with healthy versions to essentially cure genetic human diseases. So in order to further the science, Mitalipov and his colleagues wanted to test what happened when CRISPR was used in a human embryo. Theoretically, once CRISPR broke the DNA in the appropriate place to cut out a mutation, the cell’s natural repair mechanisms would kick in to repair the injury, fixing the defect this time with the proper code—much like how a word processor’s autocorrect function fixes spelling mistakes.
Unfortunately, this process isn’t very efficient in adult cells in which CRISPR has been tested, so Mitalipov expected similarly low yields in the embryos.
To his surprise, however, he found that embryos were very effective at fixing breaks in DNA.
He created embryos that contained a specific defect known to cause a heart condition by fertilizing healthy donor eggs from various women with sperm from a man who carried the genetic mutation for the disease. He then introduced CRISPR to splice out the mutated gene in more than 50 embryos just after the sperm fertilized the eggs, when the embryos were still just one cell. Several days later, 72% of the embryos showed no sign of the mutated gene; the gene was essentially corrected in all of their cells.
MORE: How the Science of CRISPR Can Change Your Genes
It turns out that the embryo relies on the normal copy of the gene, in this case from the egg, to fix the break made when CRISPR cut out the mutated gene. They key was to introduce CRISPR early enough so the embryo’s own DNA repair system could fix the mutated gene. That’s encouraging for one potential use of CRISPR in the future as a way to correct inherited genetic disease, says Mitalipov, since the embryo seems to have a built-in, reliable way of repairing the injury caused by splicing out an abnormal gene.
“Genetic diseases that are heritable can be treated this way as early as possible,” he says. “It’s the best way to treat the disease before the genetic mutation is actually transmitted to the embryo.”
MORE: New Technique That Lets Scientists Edit DNA Is Transforming Science—and Raising Difficult Questions
Currently, the most reliable way of screening for such inherited defects is by using IVF, screening the resulting embryos for the mutation and transferring only those without the mutation for pregnancy. But that may require several cycles of IVF, which is expensive and carries with it side effects and complications, before enough genetically healthy embryos are created.
The study results don’t mean that editing human embryos to correct genetic diseases will be available at hospitals anytime soon. While that’s the goal, the findings are just the first in a series of studies that will need to be done to document the safety and reliability of using CRISPR to fix human disease. For one, the efficiency of the CRISPR and repair process is still about 70%. “There is still work to do to improve the efficiency,” says Mitalopov. “But I think that’s possible to do.”
MORE: HIV Genes Have Been Cut Out of Live Animals Using CRISPR
He’s also encouraged by the fact that the gene editing and repair did not introduce other errors in the DNA. While it’s the most accurate DNA editor available, one of CRISPR’s drawbacks is that it can cut the genome in unintended places, especially where letters in the code look very similar to the target (again, similar to the way autocorrect can sometimes introduce more errors in attempting to fix a misspelling). Mitalipov’s team found no such off-target effects, a sign that CRISPR editing, at least in this study, was relatively safe. He notes, however, that may simply be an artifact of the particular gene he targeted; there may be coincidentally no parts of the genome that have similar sequences as the gene that CRISPR cut.
Even beyond the medical questions, there are also ethical concerns about the power inherent in manipulating the human genome. While correcting devastating diseases such as the heart condition Mitalipov studied, which can cause sudden death in young people, isn’t ethically controversial, using CRISPR to modify other genes—for intelligence, say, or athleticism or physical attributes like eye color or height—is much more problematic. The concerns are especially acute when it comes to eggs, sperm and embryos, since changes in these can be passed down to the next generation and forever change the human gene pool. The embryos that Mitalipov created were never intended to be transferred for pregnancy. But had they been allowed to develop, they would not contain the heart disease mutation, and they would not pass on the mutation to their offspring. The CRISPR editing would essentially eliminate the mutation from that family’s pedigree. Editing changes in already developed cells in adults aren’t inherited, so are less worrisome in terms of their legacy.
MORE: Pandora’s Baby: How A New Type Of Prenatal Genetic Testing Could Predict Your Child
For now, there are legal and regulatory hurdles to moving the research closer to human trials. The National Institutes of Health (NIH) does not provide funding for using CRISPR in human embryo research. The Food and Drug Administration is banned from considering studies that involve genetic altering of human eggs, sperm or embryos. Mitalipov and his team used funding from Oregon Health & Science and did not rely on any NIH support.
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5 Times You Really, Seriously Need to Go to the ER
Chinese scientists may have been the first to use CRISPR, a powerful new gene editing tool, to fix genetic defects in human embryos, but the first U.S. scientists to achieve the same feat say their method is more reliable.
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Thursday, July 13, 2017
FDA Panel Recommends Approval of the First Gene Therapy Treatment
This article originally appeared on Time.com.
An advisory panel for the FDA recommended approving the first gene therapy for use in the U.S., and the treatment is meant for children with B-cell acute lymphoblastic leukemia, the most common blood cancer in children. The FDA doesn’t have to follow the advice of the advisory committee, but it often does.
The new therapy, called chimeric antigen receptor T cell (CAR-T) therapy, provides new hope that the disease won’t just be treated, but cured. It’s based on using the immune system to fight against cancer—currently the most promising way to fight tumors. Cancer cells arise from normal cells, so the immune system doesn’t always recognize that anything is wrong. A pioneering group of drugs already approved by the Food and Drug Administration (FDA), called checkpoint inhibitors, remove the brakes on the immune system and allow it to attack tumor cells that it normally wouldn’t.
The newly approved therapy CAR-T therapy works to co-opt the immune system in a different way. It involves removing a patient’s blood and essentially replacing it with a population of blood cells stacked with cancer-fighting immune cells known as T cells. To do that, researchers use gene therapy to change patients’ bone marrow cells, which make blood and immune cells, to recognize cancer cells.
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Novartis applied for the approval for its drug, tisagenlecleucel, to treat acute lymphblastic leukemia in children who have exhausted all the existing treatments for the disease. Doctors say the drug, which helps to genetically engineer the cells, only needs to be infused once to repopulate children’s blood with healthy, cancer-fighting cells. In a small group of patients who have received the therapy, 83% were in complete or partial remission three months later.
MORE: Immunotherapy May Treat This Deadly Breast Cancer
“Novartis has long believed in the potential of chimeric antigen receptor T cell (CAR-T) therapies to change the cancer treatment paradigm,” the company said in a statement responding to the decision.
Other companies are also pursuing CAR-T cell strategies but have struggled with major complications. Some patients receiving CAR-T therapy can develop a severe inflammatory reaction known as cytokine release syndrome, in which the immune system is overactive and can cause high fever, neurological symptoms and organ damage. Earlier this year, Kite Pharma, which also has a CAR-T therapy product being reviewed by the FDA, reported the death of a patient from brain swelling, and Juno Therapeutics placed its CAR T program on hold when its scientists weren’t able to overcome the toxicity.
Researchers at the hearing told the advisory panel that careful monitoring for the first signs of the inflammation can keep it under control. The advisory panel determined, unanimously, 10-0, that the benefit of the therapy outweighed the risks.
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Wednesday, July 12, 2017
Wednesday, July 5, 2017
8 Ways to Spot a Narcissist
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