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Questioning unexpected CRISPR off-target mutations in vivo

By Sang-Tae Kim, Jeongbin Park, Daesik Kim, Kyoungmi Kim, Sangsu Bae, Matthias Schlesner, Jin-Soo Kim

Posted 30 Jun 2017
bioRxiv DOI: 10.1101/157925 (published DOI: 10.1038/nmeth.4554)

In summary, the CRISPR-Cas9-treated mice do not exhibit more variants that are absent in the uncorrected control than vice versa. Furthermore, the observed variants are extremely unlikely a consequence of a mutagenic process in the investigated animal, but are much better explained by differences in the genetic background between the two gene-edited mice and the control mouse. We conclude that the data presented by Schaefer et al does not provide any evidence for off-target mutagenesis due to CRISPR-Cas9 treatment and see no reason to be doubtful about the previous findings that Cas9 does not cause SNVs and indels at non-homologous, PAM-free sites.

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