4.8 Article

Supramolecular CRISPR-OFF switches with host-guest chemistry

期刊

NUCLEIC ACIDS RESEARCH
卷 50, 期 3, 页码 1241-1255

出版社

OXFORD UNIV PRESS
DOI: 10.1093/nar/gkac008

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资金

  1. National Natural Science Foundation of China [91853119, 21877086, 21871216, 21722803, 21721005, 91753201, 51873160]
  2. Hubei Provincial Natural Science Foundation [2019CFA064]
  3. Fundamental Research Funds for the Central Universities [91853119, 2042021kf0211]

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This study demonstrates the development of supramolecular CRISPR-OFF switches using host-guest chemistry, which can effectively reduce excessive activity of CRISPR complexes in human cells. The work indicates the considerable potential of the supramolecular strategy for controlling and enhancing CRISPR systems.
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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