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A preprint appearing at BioRxiv says that the sequence variants another research team attributed to the work of CRISPR/Cas9 may instead be natural variation.

In May, researchers from Stanford University reported in Nature Methods that when they deeply sequenced mice they'd used in a CRISPR/Cas9 gene-editing study, they found more mutations than they'd expected in the edited mices versus the control mouse.

As New Scientist points out, this study has been the subject of criticism and of calls for it to be withdrawn. In particular, the CRIPSR companies Editas Medicine and Intellia Therapeutics have argued in separate letters that the paper's data doesn't support its conclusions. Nature Methods has added a note to the paper saying that "the conclusions of this paper are subject to criticisms that are being considered by editors."

In the new BioRxiv preprint, researchers led by Massachusetts General Hospital's Luca Pinello say that the simplest explanation of the data in the Nature Methods study is that the two CRISPR/Cas9 edited mice were actually more related to each other than to the control mouse. "This strongly suggests that the so-called 'unexpected mutations' simply represent SNPs and indels shared in common by these mice prior to nuclease treatment," Pinello and colleagues write.

The Stanford team had assumed that the three mice in their study were basically genetically identical because their parents were closely related, New Scientist says, but Pinello's team says the way the mouse colony was maintained suggests they weren't.

New Scientist adds that this new explanation would also account for why the shared mutations among the edited mice were not located near DNA sequences were targeted by CRISPR/Cas9.

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