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[Correspondence]Response to “Unexpected mutations after CRISPR–Cas9 editing in vivo”
 Authors and Affiliations  Authors and Affiliations
Sang-Tae Kim1,7, Jeongbin Park2,3,7, Daesik Kim4, Kyoungmi Kim1, Sangsu Bae5, Matthias Schlesner2,6,* & Jin-Soo Kim1,4,*
1Center for Genome Engineering, Institute for Basic Science, Seoul, South Korea. 2Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Heidelberg, Germany. 3Faculty of Biosciences, Heidelberg University, Heidelberg, Germany. 4Department of Chemistry, Seoul National University, Seoul, South Korea. 5Department of Chemistry, Hanyang University, Seoul, South Korea. 6Bioinformatics and Omics Data Analytics, German Cancer Research Center (DKFZ), Heidelberg, Germany. 7These authors contributed equally to this work.
*Correspondence to Matthias Schlesner or Jin-Soo Kim.
Abstract
To the Editor : Recently, Schaefer et al.1 reported that whole-genome sequencing (WGS) of two Cas9-treated, gene-corrected mice and a wild-type control mouse unveiled 1,397 single-nucleotide variations (SNVs) and 117 small insertions and deletions (indels) present commonly in the two Cas9-treated mice “but absent in the uncorrected control” and from a database of mouse SNVs and indels. There was essentially no sequence homology between the on-target site and these SNVs and indel sites, most of which lacked a protospacer-adjacent motif (PAM) sequence. Nevertheless, the authors concluded that these variations were caused by CRISPR?Cas9 without validating these unexpected off-target effects in an independent experiment in vitro or in vivo.
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