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11.04.2016

Second CRISPR human embryo study shows there is a long way to go

A team in China has announced the results of their attempts to modify human embryos using the CRISPR gene-editing technique – the second study of its kind. New Scientist asks if the study can tell us anything new about gene editing in humans

What did the CRISPR study try to achieve?

A team at the Third Affiliated Hospital of Guangzhou Medical University used CRISPR to try to introduce a mutation into human embryos that makes people immune to HIV. This mutation prevents people from making the CCRF receptor that normally lets the HIV virus into a cell.

The team say they were trying to evaluate methods of precisely modifying early human embryos. But like the first study to be published on CRISPR editing in human embryos, this HIV work was done on embryos that had been rejected by IVF clinics because they had an extra set of chromosomes. Because of this, it’s far from clear whether either study can tell us much about gene-editing in healthy human embryos.

Both studies used a basic form of CRISPR, but the technology is advancing at a dizzying pace, and improved methods have already been developed. Some argue that, with CRISPR still in its infancy, it is far too soon to carry out such studies.

Did the gene editing work?

Not very well. In one experiment, 45 embryos at the one-cell stage were injected with the RNA instructions required to make the CRISPR machinery. Only 26 of these developed into eight-cell embryos or beyond, and of these, only four had the desired CCR5 mutation. And because each of these had the mutation in only one copy of the CCR5 gene, this would not be enough to confer HIV resistance. Both copies of the gene must be modified to stop the virus from being able to get into the cell.

On the plus side, the team did not find any unintended mutations in the embryos, although they only checked for these in 28 sites in the genome where they thought they were likely to occur. Such off-target mutations would be a major safety worry when applying the technique in people.

Could we make gene-edited babies today?

Yes, but not if we want to be sure they will be healthy. Like the first embryo study, the team behind the new findings have suggested there is a long way to go before we can safely edit embryos intended for implantation. “We believe that any attempt to generate genetically modified humans through the modification of early embryos needs to be strictly prohibited until we can resolve both ethical and scientific issues,” they say in their paper.

What problems are there with technique?

The biggest issue is something called mosaicism. Even in those embryos where they were able to modify the CCR5gene, not all of the cells had picked up the desired change. Had such embryos been allowed to develop further, not all of the organs and tissues in the body would have had the change, potentially leaving individuals still vulnerable to HIV. The team suggests that mosaicism from gene editing could be prevented by modifying the stem cells that give rise to eggs and sperm, instead of embryos. But this would be even more difficult.

Another problem is the failure rate: just four partial successes starting with 45 embryos. Most  couples get only one to three embryos suitable for implantation per IVF cycle, so using CRISPR as part of assisted reproduction would not be practical with success rates as low as those in this study.

Gene-editing children might be worth these risks if it was the only way to prevent serious disease, but it is not. Today, pre-implantation screening of embryos already offers a safe way to prevent children inheriting such mutations from their  parents.

What should we expect next?

Rumour has it that at least three other studies involving gene-editing human embryos have been done in China but their results have not yet been published.

Meanwhile, a human embryo study in the UK has been given the go-ahead. The aim of this project, which hasn’t yet started, is to use CRISPR to help understand how embryos develop, rather than working towards genetically modifying babies.

Journal reference: Journal of Assisted Reproduction and Genetics, DOI: 10.​1007/​s10815-016-0710-8

Read more about using gene editing to fight HIV: HIV defies attempts to edit virus out of human cells with CRISPR

Source: https://www.newscientist.com/article/2083833-second-crispr-human-embryo-study-shows-there-is-a-long-way-to-go/




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