Supramolecular CRISPR-OFF switches with host–guest chemistry |
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| Authors: | Wei Xiong Xingyu Liu Qianqian Qi Huimin Ji Fengbo Liu Cheng Zhong Simin Liu Tian Tian Xiang Zhou |
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| Affiliation: | 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;School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan 430081, Hubei, China |
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| 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. |
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