Major Genetic breakthrough could curb thousands of hereditary diseases

Shoukhrat Mitalipov is the first U.S.-based scientist known to have edited the DNA of human embryos.		
	OHSU  Kristyna Wentz-Graff

US scientists are calling for a rethink of current restrictions on using CRISPR/Cas9 gene editing in human embryos after successfully correcting the MYBPC3 hypertrophic cardiomyopathy mutation, the commonest cause of heart failure and sudden death in apparently healthy young people, without causing any off-target effects or mosaicism.

Dr Shoukhrat Mitalipov, from Oregon Health and Science University (OHSU) in Portland, said "Every generation on would carry this fix because we have removed the disease-causing gene variant from that family's lineage".

Says co-author Jun Wu of the Salk Institute in San Diego: "Our technology successfully repairs the disease-causing gene mutation by taking advantage of a DNA fix response unique to early embryos".

The technique, if commercialized after clinical tests, is expected to help prevent many genetic diseases by correcting disease-causing mutation at the stage of artificial insemination. The scientists made the gene edits early in the embryos' development and saw the efficiency of DNA correction go up.

Experts have hailed research raising the prospect of Britain pioneering the use of human embryo gene editing to wipe out inherited diseases as "remarkable" and a "major advance". "Clinical trials would mean actually implanting some of these embryos with the goal of establishing pregnancy and monitoring births of children and hopefully following up with children". As a result, only 28% of the resulting embryos carried genes for hypertrophic cardiomyopathy.

Darren Griffin, a professor of genetics at the University of Kent, said: "Perhaps the biggest question, and probably the one that will be debated the most, is whether we should be physically altering the genes of an IVF embryo at all". At the time, details were sparse: CRISPR, the ground-breaking gene-editing technique was employed, and the embryos were terminated after a few days. In Nature, Oregon Health and Science University (OHSU) researchers outlined their achievement, which opens a door into a long-awaited, controversial future in which "designer babies" are a very real possibility.

The first published work involving human embryos, reported in 2015, was done in China and targeted a gene that leads to the blood disorder beta thalassemia.

THE NEWS that researchers have carried out the first known attempt to create genetically modified human embryos is another signpost in an astounding revolution unfolding before our eyes.

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"Looking at it more closely, it's less useful than you might expect, if it works at all", Greely said. The same technique could be used against genes that cause thousands of diseases, including some breast and ovarian cancers. 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.

The practice of germline editing using CRISPR is still hotly contested, however.

"None of the embryos we generated in this study were for reproductive purposes but if they were, the idea is that they wouldn't carry this mutation so the parents wouldn't have to worry about transferring this to their children, said Mitalipov". In the US, Congress has barred the Food and Drug Administration from even considering human trials with edited embryos, while in the United Kingdom it is illegal to implant genetically modified embryos in women. In this particular experiment, the researchers used CRISPR-Cas9 on 58 embryos containing the mutation. One woman she treated recently underwent three cycles of IVF but no embryos suitable for implantation were generated.

More importantly, CRISPR-Cas9 has the potential to prevent a myriad of diseases and conditions beyond hypertrophic cardiomyopathy, which affects about 1 in 500 people.

As detailed in the paper's research methods, the scientists adhered to strict ethical guidelines, and were monitored closely by committees of individuals including not just scientists and doctors, but also members of the general public.

Professor Robin Lovell-Badge from the Francis Crick Institute said that the research only appears to work when the father is carrying the defective gene, and that it would not work for more sophisticated alterations.

The study was reviewed by an internal board at OHSU, and the team says they were working within the guidelines of the recently released National Academy of Sciences guidelines. "There is still a long road ahead, and it's unclear at this point when we will be allowed to move on".

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