A large CRISPR-induced bystander mutation causes immune dysregulation.
Ontology highlight
ABSTRACT:
SUBMITTER: Simeonov DR
PROVIDER: S-EPMC6379443 | biostudies-literature | 2019
REPOSITORIES: biostudies-literature
Publications
A large CRISPR-induced bystander mutation causes immune dysregulation.
Simeonov Dimitre R DR Brandt Alexander J AJ Chan Alice Y AY Cortez Jessica T JT Li Zhongmei Z Woo Jonathan M JM Lee Youjin Y Carvalho Claudia M B CMB Indart Alyssa C AC Roth Theodore L TL Zou James J May Andrew P AP Lupski James R JR Anderson Mark S MS Buaas F William FW Rokhsar Daniel S DS Marson Alexander A
Communications biology 20190218
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 target ...[more]
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