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In Gene-Editing Advance, Scientists Correct Defect in Human Embryos

For the first time in the U.S., researchers said they had edited viable human embryos to correct a disease-causing defect, avoiding problems that plagued previous efforts and stoking concerns that advances in the lab are outpacing public discussion about the ethics of gene editing.

Using the gene-editing tool Crispr-Cas9, the researchers said they successfully corrected a mutation that can cause a heart condition called hypertrophic cardiomyopathy, or HCM. The condition, affecting an estimated 1 in 500 people, is best known as a common cause of sudden cardiac death in young athletes.

The collaboration, led by researchers at Oregon Health & Science University, the Salk Institute for Biological Studies and Korea’s Institute for Basic Science, used embryos created from healthy egg donors and sperm donated by an adult male who has the gene mutation and a family history of HCM. The donors were recruited in Oregon, and the gene editing was done in the U.S., according to a spokesman for OHSU.

Images show the development of embryos after co-injection of a gene-correcting enzyme and sperm from a donor with a genetic mutation known to cause hypertrophic cardiomyopathy. PHOTO: OREGON HEALTH & SCIENCE UNIVERSITY


The embryos, created for research, weren’t implanted in a woman, according to the researchers, who reported their findings Wednesday in the journal Nature.

The study results raise ethical questions because they involve changes to the human germ-line, the genes of sperm, eggs or embryos. Scientists and bioethicists have called for caution in editing the germ-line because such changes would not only alter the individual but also be passed to future generations.

Regulatory agencies have been willing to consider testing Crispr-Cas9 therapies that treat diseases in individuals. But the U.S. Food and Drug Administration is prohibited by law from using funds to accept applications for research using gene editing of the human germ-line.

A report published this year from an international ethics committee sponsored by the U.S. National Academy of Sciences and the National Academy of Medicine concluded that germ-line editing might someday be permitted, with limits. Among the committee’s recommendations were that the technique be used to treat only serious conditions and only when other options aren’t available.

Once studies are published in the scientific literature, other groups try to replicate them. Some countries might permit the work eventually to move forward to clinical trials. A U.K. fertility regulatory authority granted permission to researchers editing human embryos with Crispr for research purposes. Chinese scientists have pushed ahead with Crispr research in human embryos.

Jeffrey Kahn, director of the Johns Hopkins Berman Institute of Bioethics and a member of the National Academy committee, said this new paper is “pushing hard on the international conversation.” An international summit on gene editing is scheduled for early 2018 in Shanghai or Beijing, he said.

There is disagreement among this study’s researchers about how quickly such research should move forward.

Juan Carlos Izpisua Belmonte, a professor in Salk’s Gene Expression Laboratory, a corresponding author of the paper and a member of the international ethics committee, said the results are promising but “the research should stay in the lab where scientists can improve the technologies.”

Shoukhrat Mitalipov, a senior author of the paper from Oregon Health, said although more work needs to be done to replicate the results, his goal is to have clinical trials involving the transfer of embryos into the womb to produce pregnancy and the birth of healthy children.

He didn’t rule out the possibility of trials in other places such as the U.K.“We would like to do regulated clinical trials,” said Dr. Mitalipov. He worries U.S. prohibitions might lead to the technology’s use in “unregulated areas, which should not be happening.”

The Crispr system works by targeting a specific spot in DNA and cutting it. Healthy DNA can then be used to replace the faulty gene when the cell repairs the cut. The technology holds great promise for treating many diseases.

The technology has sparked a rush of investment into companies poised to take advantage of Crispr. Hundreds of millions of dollars have been invested in for-profit startups founded by scientists whose academic institutions are now warring with each other over the patent.

Previous experiments have run into problems. Sometimes the Crispr system made cuts in unintended spots of the DNA, which can potentially introduce other health issues. Other concerns occur when only some of the embryo cells are repaired, called mosaicism.

By experimenting at an early stage, researchers in the Nature study avoided some of those issues and reported they corrected the mutation in 42 of 58 embryos, or 72.4%. They were able almost to eliminate mosaicism except in one embryo.

Some scientists caution it is still far too early to move out of the lab. “They got 72% of what they wanted, which is way better than what anyone has seen before but is not good enough,” said Paul Knoepfler, a stem cell biologist at UC Davis School of Medicine. “You need to be close to perfect to really ever try this in an actual human reproductive context.”