Cytosine base editor generates substantial off-target single-nucleotide variants in mouse embryos

• DOI: 10.1126/science.aav9973
• Publication Date: 2019-03-01T00:15:18Z
• Authors: Erwei Zuo; Yidi Sun; Wu Wei; Tanglong Yuan; Wenqin Ying; Hao Sun; Liyun Yuan; Lars M. Steinmetz; Yixue Li; Hui Yang
• Keywords: Blastomere; Cytosine

Spotting off-targets from gene editing Unintended genomic modifications limit the potential therapeutic use of gene-editing tools. Available methods to find generally do not work in vivo or detect single-nucleotide changes. Three papers this issue report new for monitoring tools (see Perspective by Kempton and Qi). Wienert et al. followed recruitment a DNA repair protein breaks induced CRISPR-Cas9, enabling unbiased detection off-target cellular animal models. Zuo identified without interference natural genetic heterogeneity injecting base editors into one blastomere two-cell mouse embryo leaving other genetically identical unedited. Jin performed whole-genome sequencing on individual, genome-edited rice plants identify unintended mutations. Cytosine, but adenine, numerous variants both rice. Science , p. 286 289 292 ; see also 234