Biomedical Sciences Graduate Program, University of California, San Francisco, CA, 94143, USA.
Department of Microbiology and Immunology, University of California, San Francisco, CA, 94143, USA.
Commun Biol. 2019 Feb 18;2:70. doi: 10.1038/s42003-019-0321-x. eCollection 2019.
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.
人们一直对 CRISPR-Cas9 基因编辑技术存在担忧，担心其可能会在非靶标基因组位点产生突变。在对 CRISPR 编辑的小鼠进行研究以删除一个约 360bp 的内含子增强子时，我们发现一个创始系由于紧邻靶标缺失序列的 24kb 串联重复而出现明显的免疫失调。我们的结果表明，靶标基因组切割的意外修复可能导致致病的“旁观者”突变，而这些突变会逃避常规的靶向基因分型检测。
