DR YORGOS NIKAS/SCIENCE PHOTO LIBRARY
The results of a much-publicised study claiming mutations in human embryos can be safely corrected with CRISPR have been called into question by other researchers.
The team behind the work say they stand by their findings, but at the very least the dispute shows there are still major issues that need to be resolved before anyone should attempt to use gene-editing to prevent children inheriting disease-causing mutations.
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“There are lots of unanswered questions,” says embryologist Anthony Perry of the University of Bath in the UK.
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The first studies to try using the CRISPR genome-editing technique to alter the DNA of human embryos revealed several major problems. For instance, it only corrected mutations in a small proportion of embryos.
Last month, however, a team led by Shoukhrat Mitalipov of Oregon Health and Science University claimed they had managed to improve efficiency while avoiding other key problems such as unwanted alterations. The study was widely proclaimed as a breakthrough.
Now doubts have been raised. Genome editing works by breaking DNA, and letting a cell’s natural repair mechanisms fix it. This is usually quite haphazard, and precise repairs were thought to be rare.
Correction or deletion?
But when Mitalipov’s team used CRISPR to try fixing a mutation that causes heart disease, they reported getting precise repairs in most of the embryos they tried it on.
The team have claimed they have discovered a novel DNA repair mechanism in embryos, which uses egg DNA as a template for repairing the embryo’s DNA that originally came from sperm.
If this were true, it would mean we could only use CRISPR to alter paternal DNA in an embryo. And we would only be able to make changes that matched gene sequences already present in a mother’s genome.
But Perry found no evidence of such a repair mechanism in similar experiments carried out in mice back in 2014. What’s more, it doesn’t make sense. At the stage when the repair is supposed to take place, Perry says, there is considerable distance between the paternal and maternal DNA.
According to the renowned biologist George Church of Harvard University and his colleagues, Mitalipov’s team may not have corrected the heart disease mutation at all. In a critique published this week, Church and his colleagues say the team have merely shown that the mutation was absent – this could be caused by deleting DNA, rather than repairing it, they argue.
Young technology
If Church and his team are right, this would be bad news for editing human embryos – deleting bits of DNA is not a desirable thing to do. Mitalipov’s team say they will publish a formal response to the critique in coming weeks.
However, the long-term prospects for genome editing remain bright. The CRISPR approach is still only a few years old, and the technology is advancing fast. And editing embryos is not the only option – it might be safer to alter sperm or eggs instead.
As ever, it is worth nothing that the vast majority of genetic diseases caused by a single mutation can already be safely prevented by screening IVF embryos before implantation. The real promise of CRISPR lies in its potential for making multiple changes.
Journal reference: bioRxiv, DOI: 10.1101/181255
Read more: Editing life: A guide to the genetic revolution on our doorstep
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