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Back and Forth on CRISPR Paper Critiques

When Oregon State Health and Science University researchers led by Shoukhrat Mitalipov reported last year that they had used the gene-editing tool CRISPR/Cas9 to correct a heart disease mutation in viable human embryos, critics were skeptical.

As Technology Review reports, those critics have been given a platform at Nature, which published Mitalipov and his colleagues' report last year, to air their concerns. Memorial Sloan Kettering Cancer Center's Maria Jasin and her colleagues, who first critiqued the work in a preprint at BioRxiv, questioned the paper's conclusion that the paternal allele was corrected via inter-homologue homologous recombination using the maternal allele as a repair template. They note that at the stage that this repair was to have taken place, the parental genomes are in separate pronuclei. Jasin and her colleagues instead suspect that the swathe of DNA to be corrected was actually deleted from the paternal genome.

Similarly, in a separate commentary, the University of Adelaide's Paul Thomas and his colleagues write that they also suspect that Mitalipov and his colleagues actually deleted a chunk of the paternal genome, which then prevented them from detecting that allele. They report that when they used a similar approach in mice, they generated deletions.

Mitalipov and his colleagues respond to these critiques and say that in late mammalian zygotes, the maternal and paternal pronuclei move closer together and then come into contact, which would then allow that type of repair to occur. They also add that they have since examined using PCR whether large deletions occurred, but did not detect any. However, Adelaide's Fatwa Adikusuma, one of Thomas' co-authors, notes at Wired that using qPCR might've been a better approach.

Thomas adds at Nature that the criticisms likely won't be laid to rest until other labs try to edit human embryos. "That will probably take some time. By their nature, these experiments are strictly regulated or not permitted in some jurisdictions," he says.