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bioRxiv · 10.1101/154450

Response to Editas: Unexpected mutations after CRISPR-Cas9 editing in vivo

Schaefer, K. A.·Wu, W.-H.·Colgan, D. F.·Tsang, S. H.·Bassuk, A. G.·Mahajan, V. B.
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Abstract

Our previous publication suggested CRISPR-Cas9 editing at the zygotic stage might unexpectedly introduce a multitude of subtle but unintended mutations, an interpretation that not surprisingly raised numerous questions. The key issue is that since parental lines were not available, might the reported variants have been inherited? To expand upon the limited available whole genome data on whether CRISPR-edited mice show more genetic variation, whole-genome sequencing was performed on two other mouse lines that had undergone a CRISPR-editing procedure. Again, parents were not available for either the Capn5 nor Fblim1 CRISPR-edited mouse lines, so strain controls were examined. Additionally, we also include verification of variants detected in the initial mouse line. Taken together, these whole-genome-sequencing-level results support the idea that in specific cases, CRISPR-Cas9 editing can precisely edit the genome at the organismal level and may not introduce numerous, unintended, off-target mutations.

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Schaefer, K. A., Wu, W.-H., Colgan, D. F., Tsang, S. H., Bassuk, A. G., Mahajan, V. B.. 2017-06-23. Response to Editas: Unexpected mutations after CRISPR-Cas9 editing in vivo. https://doi.org/10.1101/154450

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