Key Laboratory of Biomedical Polymers of Ministry of Education, College of Chemistry and Molecular Sciences, The Institute of Molecular Medicine, Wuhan University People's Hospital, Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University, Wuhan 430072, Hubei, China.
State Key Laboratory of Analytical Chemistry for Life Sciences, School of Chemistry and Chemical Engineering, Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing 210023, China.
Cell Chem Biol. 2024 Oct 17;31(10):1839-1851.e8. doi: 10.1016/j.chembiol.2024.09.006. Epub 2024 Oct 8.
A photocatalytic click chemistry approach, offering a significant advancement over conventional methods in RNA function modulation is described. This innovative method, utilizing light-activated small molecules, provides a high level of precision and control in RNA regulation, particularly effective in intricate cellular processes. By applying this strategy to CRISPR-Cas9 gene editing, we demonstrate its effectiveness in enhancing gene editing specificity and markedly reducing off-target effects. Our approach employs a vinyl ether modification in RNA, which activated under visible light with a phenanthrenequinone derivative, creating a CRISPR-OFF switch that precisely regulates CRISPR system activity. This method not only represents an advancement in genomic interventions but also offers broad applications in gene regulation, paving the way for safer and more reliable gene editing in therapeutic genomics.
描述了一种光催化点击化学方法，该方法在 RNA 功能调节方面相较于传统方法有重大突破。这种创新方法利用光激活的小分子，在 RNA 调控方面提供了高度的精确性和可控性，在复杂的细胞过程中特别有效。通过将该策略应用于 CRISPR-Cas9 基因编辑，我们证明了它在提高基因编辑特异性和显著降低脱靶效应方面的有效性。我们的方法在 RNA 中采用乙烯基醚修饰，该修饰在可见光下被一种菲醌衍生物激活，形成 CRISPR-OFF 开关，可精确调节 CRISPR 系统的活性。这种方法不仅代表了基因组干预方面的一项进展，而且在基因调控方面也有广泛的应用，为治疗性基因组学中更安全、更可靠的基因编辑铺平了道路。
