Commun Biol 2019 Feb 18; 2:70
A persistent concern with CRISPR-Cas9 gene editing has been the potential to generate mutations at off-target genomic sites. While CRISPR-engineering mice to delete a ~360 bp intronic enhancer, here we discovered a founder line that had marked immune dysregulation caused by a 24 kb tandem duplication of the sequence adjacent to the on-target deletion. Our results suggest unintended repair of on-target genomic cuts can cause pathogenic "bystander" mutations that escape detection by routine targeted genotyping assays.
Simeonov, Dimitre R; Brandt, Alexander J; Chan, Alice Y; Cortez, Jessica T; Li, Zhongmei; Woo, Jonathan M; Lee, Youjin; Carvalho, Claudia M B; Indart, Alyssa C; Roth, Theodore L; Zou, James; May, Andrew P; Lupski, James R; Anderson, Mark S; Buaas, F William; Rokhsar, Daniel S; and Marson, Alexander, "A large CRISPR-induced bystander mutation causes immune dysregulation." (2019). Faculty Research 2019. 47.