Tuesday, 17 October, 2017

Deadly gene mutations removed from human embryos in landmark study

First human embryos edited in the USA. Here's why it's problematic. Scientists Are Shocked About How Easy It Is To Tweak Genes In Human Embryos
Patty Aguilar | 03 August, 2017, 15:41

Scientists in the United States reached a new milestone by successfully altering DNA in defective embryos so they were no longer programmed to develop heart failure.

There's wide agreement that more research is needed on the technology itself as well as its ethical implications.

HUMAN embryos have been successfully gene edited to remove a killer mutation in a world first. Mitalipov's team found no such off-target effects, a sign that CRISPR editing, at least in this study, was relatively safe.

But this new work suggests that gene research is moving faster than the National Academies anticipated, and might soon outpace our efforts to regulate it.

Developmental biologist Robin Lovell-Badge of the Francis Crick Institute in London shares those concerns. It's a big step toward one day preventing a list of inherited diseases.

It is the first time that human embryos have had their genomes edited outside China, where researchers have performed a handful of small studies to see whether the approach could prevent inherited diseases from being passed on from one generation to the next.

But scientists behind the study, published in the journal Nature, said Britain could pioneer future research. 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. "Whilst we are just beginning to understand the complexity of genetic disease, gene-editing will likely become acceptable when its potential benefits, both to individuals and to the broader society, exceeds its risks".

Then they used the man's sperm to fertilize eggs from 12 female donors - injecting CRISPR at the same time.

James Adjaye, chair of stem cell research and regenerative medicine, Heinrich Heine University, Dusseldorf, Germany, said it is "a major and unexpected observation" that the DNA fix mechanism in early embryos seems to be different from that in human iPSC cells and maybe even somatic cells. Think of it as a biological cut-and-paste program. She is an adjunct associate professor of obstetrics and gynecology at Oregon Health & Science University (OHSU) in Portland. Using this method, they were able to achieve a high yield of homozygous embryos carrying the wild-type MYBPC3 gene without evidence of off-target mutations.

Importantly, they still must make sure that their gene-editing technique doesn't cause inadvertent mutations elsewhere in the embryo. An embryo who experiences gene modification could also carry and pass on edited genes. The study authors assumed this would be the best time for genome editing to occur, as the sperm at that time only has a single mutant copy. Beginning the process before fertilization avoided that problem: Until now, "everybody was injecting too late", Mitalipov said.

"This research significantly advances scientific understanding of the procedures that would be necessary to ensure the safety and efficacy of germline gene correction", said Daniel Dorsa, Ph.D., senior vice president for research at Oregon Health & Science University (OHSU), in a press statement. If US regulators - the Food and Drug Administration - weren't willing to let that happen, the scientists say they'd pursue clinical trials overseas, perhaps in the United Kingdom or elsewhere.

"Looking at it more closely, it's less useful than you might expect, if it works at all", Greely said. That research is aimed at understanding basic reproductive and developmental biology, as well as unpicking some of the causes of early miscarriages. If not, "this technology will be shifted to unregulated areas, which shouldn't be happening", he explained.

Among key questions: Would the technique work if mom, not dad, harbored the mutation? CRISPR cut out the MYBPC gene and replaced it with a healthy gene from the mother.

Dr Yalda Jamshidi, of St George's, University of London, said: "Families with genetic diseases have a strong drive to find cures".

In fact, Mitalipov said the research should offer critics some reassurance: If embryos prefer self-repair, it would be extremely hard to add traits for "designer babies" rather than just eliminate disease.

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