First embryo gene-repair holds promise for inherited disease

The landmark study, first revealed in The Scotsman's sister paper the i last week, came after scientists in the USA reached a milestone by successfully altering DNA in defective embryos so they were no longer programmed to develop heart failure. But the scientists say they're confident they can push that number much higher. Work with skin cells reprogrammed to mimic embryos had suggested the mutation would be repaired in fewer than 30 percent of cells.

The technique worked on three quarters of the 58 embryos it was tried on.

"This research significantly advances scientific understanding of the procedures that would be necessary to ensure the safety and efficacy of germline gene correction", says Daniel Dorsa, senior vice president for research at Oregon Health and Science University.

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.

In a lab dish, the researchers used CRISPR, a gene-editing technique, to remove the harmful MYBPC3 mutation from the human zygotes. In a 2015 statement regarding its policy against funding research on gene-editing in human embryos, the National Institutes of Health said germline editing "has been viewed nearly universally as a line that should not be crossed".

A similar experiment had been conducted in China in 2015, but with mixed results. Essentially, the process uses genetic techniques to target sequences of DNA inside the mutant gene. In 13 embryos, only a portion of cells had been edited. Natural DNA-repair mechanisms in the cell follow up by filling in the missing pieces. Additionally, the National Institutes of Health, which is an important source of science research funding in the United States, will not financially support research on gene editing of embryos. In the designer baby-filled future Darnovsky is concerned about, the line between therapeutic and augmentative gene edits is blurred.

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"We have demonstrated the possibility to correct mutations in a human embryo in a safe way and with a certain degree of efficiency."

". Approximately one in 500 people globally suffer from hypertrophic cardiomyopathy. HCM, while not a uniformly fatal condition, has a tremendous impact on the lives of individuals, including physiological (heart failure and arrhythmias), psychological (limited activity and fear of sudden death), and genealogical concerns.

The scientists targeted a mutation in the gene MYBPC3. Doctors can treat symptoms of the condition, but there is no cure.

The procedure was most effective when CRISPR-Cas9 was injected into the eggs along with the sperm rather than immediately after.

The result: an embryo with two healthy copies of the gene that, if implanted in a woman and allowed to gestate, should result in a baby free from risk of hereditary cardiomyopathy.

Because those children would inherit the same altered genes - a biologic process known as germline editing - some bioethicists have raised questions about its effects on human evolution more broadly. They were able to correct the defect in an astonishing two thirds of embryos, all without causing a mutation that could prove unsafe. But the finding could be good news for those concerned about designer babies, because embryos may reject attempts to add new traits. It also produces mosaic embryos where some cells get fixed, others don't.

"The NAS report came out strongly against any form of gene editing created to simply enhance human potential", she added.

"At this stage, I would say this is still basic research", Wu said.

None of the tested embryos showed any signs that Cas9 was cutting where it shouldn't be.

Fr. Pacholczyk also stressed the importance of limiting gene editing to therapeutic purposes, with the subject's best interests in mind.

With further improvement, said study co-author Paula Amato of the Oregon Health & Science University, the method "can potentially be used to prevent transmission of genetic disease to future generations". "We need to be sure this can be done reproducibly and effectively".

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