Chemical Control of CRISPR Gene Editing via Conditional Diacylation Crosslinking of Guide RNAs

Author:

Lei Huajun1,Zeng Tianying1,Ye Xiaofang1,Fan Ruochen1,Xiong Wei1,Tian Tian1ORCID,Zhou Xiang1

Affiliation:

1. College of Chemistry and Molecular Sciences Key Laboratory of Biomedical Polymers of Ministry of Education The Institute of Molecular Medicine Wuhan University People's Hospital Hubei Province Key Laboratory of Allergy and Immunology Wuhan University Wuhan Hubei 430072 China

Abstract

AbstractConditional control of RNA structure and function has emerged as an effective toolkit. Here, a strategy based on a one‐step introduction of diacylation linkers and azide groups on the 2′‐OH of RNA is advance. Selected from eight phosphine reagents, it is found that 2‐(diphenylphosphino)ethylamine has excellent performance in reducing azides via a Staudinger reduction to obtain the original RNA. It is demonstrated that the enzymatic activities of Cas13 and Cas9 can be regulated by chemically modified guide RNAs, and further achieved ligand‐induced gene editing in living cells by a controllable CRISPR/Cas9 system.

Funder

National Natural Science Foundation of China

Fundamental Research Funds for the Central Universities

Publisher

Wiley

Subject

General Physics and Astronomy,General Engineering,Biochemistry, Genetics and Molecular Biology (miscellaneous),General Materials Science,General Chemical Engineering,Medicine (miscellaneous)

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