[Correspondence]Response to “Unexpected mutations after CRISPR–Cas9 editing in vivo”
Authors and Affiliations
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.