基于主客体化学的超分子 CRISPR-OFF 开关。
Supramolecular CRISPR-OFF switches with host-guest chemistry.
机构信息
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.
出版信息
Nucleic Acids Res. 2022 Feb 22;50(3):1241-1255. doi: 10.1093/nar/gkac008.
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.
CRISPR（Clustered Regularly Interspaced Short Palindromic Repeat）技术是生物学和医学领域的强大工具。然而，CRISPR 机器的过度活跃阻碍了这项技术的安全性和应用。开发在人类细胞中关闭 CRISPR 活性的方法尤为重要。本研究通过利用主体-客体化学展示了超分子 CRISPR-OFF 开关的概念。我们证明 CRISPR 系统对向导 RNA（gRNA）上的金刚烷酰化具有相当大的耐受性，而超分子络合极大地影响了金刚烷酰 gRNA 的功能。主体-客体化学被证明是减少人类细胞中 CRISPR 复合物不必要的过度活性的新型有效工具。这项工作表明，超分子策略在控制和增强 CRISPR 系统方面具有相当大的潜力。
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