Synthetic Oligonucleotides Inhibit CRISPR-Cpf1-Mediated Genome Editing.
作者： Bin Li , Chunxi Zeng , Wenqing Li , Xinfu Zhang , Xiao Luo
DOI: 10.1016/J.CELREP.2018.11.079
关键词:
摘要: Summary Previously, researchers discovered a series of anti-CRISPR proteins that inhibit CRISPR-Cas activity, such as Cas9 and Cpf1 (Cas12a). Herein, we constructed crRNA variants consisting chemically modified DNA-crRNA RNA-crRNA duplexes identified phosphorothioate (PS)-modified duplex completely blocked the function Cpf1. More important, without prehybridization, these PS-modified DNA oligonucleotides showed ability to suppress double-strand breaks induced by two orthologs, AsCpf1 LbCpf1. Time-dependent inhibitory effects were validated in multiple loci different human cells. Further studies demonstrated able serve inhibitors in a sequence-independent manner. Mechanistic indicate hinder target binding recognition Consequently, synthetic molecules expand sources CRISPR inhibitors, providing a platform inactivate Cpf1-mediated genome editing.
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