Supramolecular CRISPR-OFF switches with host-guest chemistry

Wei Xiong; Xingyu Liu; Qianqian Qi; Huimin Ji; Fengbo Liu; Cheng Zhong; Simin Liu; Tian Tian; Xiang Zhou

doi:10.1093/nar/gkac008

Supramolecular CRISPR-OFF switches with host-guest chemistry

Nucleic Acids Res. 2022 Feb 22;50(3):1241-1255. doi: 10.1093/nar/gkac008.

Authors

Wei Xiong¹, Xingyu Liu¹, Qianqian Qi¹, Huimin Ji¹, Fengbo Liu², Cheng Zhong¹, Simin Liu², Tian Tian¹, Xiang Zhou¹

Affiliations

¹ Key Laboratory of Biomedical Polymers of Ministry of Education, College of Chemistry and Molecular Sciences, Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University, Wuhan 430072, Hubei, China.
² School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan 430081, Hubei, China.

Abstract

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeat) technology is a powerful tool in biology and medicine. However, the safety and application of this technology is hampered by excessive activity of CRISPR machinery. It is particularly important to develop methods for switching off CRISPR activity in human cells. The current study demonstrates the concept of supramolecular CRISPR-OFF switches by employing host-guest chemistry. We demonstrate that the CRISPR systems show considerable tolerance to adamantoylation on guide RNAs (gRNAs), whereas supramolecular complexation tremendously affects the function of adamantoyl gRNAs. Host-guest chemistry is demonstrated to be novel and effective tools to reduce unwanted excessive activities of CRISPR complexes in human cells. This work indicates considerable potential of supramolecular strategy for controlling and enhancing CRISPR systems.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

CRISPR-Cas Systems
Clustered Regularly Interspaced Short Palindromic Repeats* / genetics
Gene Editing* / methods
Humans
RNA, Guide, CRISPR-Cas Systems / genetics

Substances

RNA, Guide, CRISPR-Cas Systems