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takyon writes:

Skepticism surfaces over CRISPR human embryo editing claims

When the first U.S. team to edit human embryos with CRISPR revealed their success earlier this month, the field reeled with the possibility that the gene-editing technique might soon produce children free of their parents' genetic defects. But the way CRISPR repaired the paternal mutation targeted in the embryos was also a surprise. Instead of replacing the gene defect with strands of DNA that the researchers inserted, the embryos appeared to use the mother's healthy gene as a template for repairing the cut made by CRISPR's enzyme.

But such a feat has not been observed in previous CRISPR experiments, and some scientists are now questioning whether the repairs really happened that way. In a paper published online this week on the preprint server bioRxiv, a group of six geneticists, developmental biologists, and stem cell researchers offers alternative explanations for the results. And uncertainty about exactly how the embryos' DNA changed after editing leaves many questions about the technique's safety, they argue. (The authors declined to discuss the paper while it's being reviewed for publication.)

Embryologist Shoukhrat Mitalipov of Oregon Health and Science University in Portland, who led the now-disputed experiments, released a statement saying that his team stands by its explanation. "We based our finding and conclusions on careful experimental design involving hundreds of human embryos," it says.

[...] Although the researchers inserted short strands of DNA as templates for repair, the cells didn't seem to take them up; those specific sequences were absent from the embryos. The cells must have relied instead on the nonmutated sequence in the egg donor's DNA when making the repairs, the team concluded.

The bioRxiv response, led by developmental biologist Maria Jasin of Memorial Sloan Kettering Cancer Center in New York City and Columbia University stem cell biologist Dieter Egli, challenges that interpretation. The authors, which also include well-known CRISPR researcher and Harvard University geneticist George Church, say that the Nature paper goes against conventional wisdom about how embryos are organized early in development. Right after an egg is fertilized, the DNA from the sperm and the egg aren't believed to be in close enough proximity to interact or share genes, they explain.

Previously: First Known Attempt at Genetically Modifying Human Embryos in the U.S. is an Apparent Success
U.S. Human Embryo Editing Study Published

Study in question: Correction of a pathogenic gene mutation in human embryos (open, DOI: 10.1038/nature23305) (DX)

Original Submission