大规模 CRISPR 诱导的旁观者突变导致免疫失调。
A large CRISPR-induced bystander mutation causes immune dysregulation.
机构信息
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.
出版信息
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。
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