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This sequence of images shows the development of embryos after co-injection of a gene-correcting enzyme and sperm from a donor with a genetic mutation known to cause a type of heart disease known as hypertrophic cardiomyopathy. (OHSU Photo)

Researchers from Oregon Health and Science University provided the details today on an experiment with human embryos that demonstrated how gene editing can repair a genetic flaw linked to heart disease.

The outlines of the experiment were reported last week, but the OHSU team held off on providing the details until today’s publication of the study in the journal Nature.

The team, led by OHSU senior researcher Shoukhrat Mitalipov, took advantage of a technique known as CRISPR-Cas9, which uses RNA guide molecules and enzymes to make targeted cuts in the DNA molecules that contain the human genetic code. Revised code can then be inserted into the snipped DNA.

The Nature study revealed that the team was able to fix a genetic mutation that causes hypertrophic cardiomyopathy, a common disease that can cause sudden heart failure and death.

“Every generation on would carry this repair, because we’ve removed the disease-causing gene variant from that family’s lineage,” Mitalipov, who directs OHSU’s Center for Embryonic Cell and Gene Therapy said in a news release. “By using this technique, it’s possible to reduce the burden of this heritable disease on the family and eventually the human population.”

Shoukhrat Mitalipov
Shoukhrat Mitalipov is the principal investigator for the Center for Embryonic Cell and Gene Therapy at the Oregon Health and Science University. (OHSU Photo / Kristyna Wentz-Graff)

The technique increased the success rate for removal of the gene variant from the expected 50-50 chance to 72 percent – that is, 42 out of 58 embryos tested. None of the embryos was implanted for pregnancy.

It’s far too early to use the technique as a treatment for the disease, which affects about 1 in 500 people. But the experiment does demonstrate that gene editing has the potential to eradicate genetic illnesses for good.

It also throws a spotlight on the ethical concerns raised by germline gene editing. If it becomes feasible to make changes in the human genome that can be passed down from generation to generation, it could become theoretically possible to produce designer babies, or even an entire subspecies of enhanced humans or supersoldiers.

The scope of the research to date is far more limited: In earlier experiments, Chinese scientists were able to make changes to the genetic code of human embryos, but there was a high incidence of off-target effects. Also, the embryos exhibited signs of mosaicism – a mishmash of genetically altered and unaltered cells.

OHSU’s team found that they were able to get around those problems by injecting the CRISPR-Cas9 molecular tool into a human egg at the same time that it was being fertilized by sperm.

The sperm came from men who carried the genetic defect linked to heart disease, in a mutated version of a gene known as MYBPC3. If one version of the bad gene is inherited, that carries the disease forward to the next generation.

During the OHSU experiment, the CRISPR-Cas9 tool cut out the bad gene – and then the embryo replaced it with a copy of the good gene it had inherited from the mother.

It’s currently illegal in the U.S. and many countries to implant a gene-edited embryo into a mother’s womb to produce a baby. “It’s unclear at this point when we would be able to move on,” Mitalipov told reporters.

However, if the procedure is proven safe, regulators could conceivable give the go-ahead to edit genetic defects out of human embryos during in-vitro fertilization, and then let those embryos be implanted. That would raise the chances of having healthy babies for millions of would-be parents who carry potentially harmful genetic mutations.

The work at OHSU “represents an important first step in ensuring that any eventual use of germline gene editing for the clinical correction of serious genetic disease can be pursued safely and effectively,” said S. Malia Fullerton, a bioethicist at the University of Washington School of Medicine.

“The fact that an unanticipated form of DNA repair was observed demonstrates the importance of such early stage research, which was ratified by the National Academies in their report last year,” Fullerton told GeekWire in an email. “Of course, even as the science moves forward, there will still be a need for ongoing societal discussion and debate about the kinds of genetic corrections that should be allowed or perhaps even promoted.”

In addition to Mitalipov, 30 other authors contributed to the Nature study, “Correction of a Pathogenic Gene Mutation in Human Embryos.”

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