Zhang Kaisong, Shen Wei, Zhao Yunting, Xu Xinyan, Liu Xingyu, Qi Qianqian, Huang Siqi, Tian Tian, Zhou Xiang
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.
Nucleic Acids Res. 2025 Feb 8;53(4). doi: 10.1093/nar/gkaf082.
In contrast to traditional RNA regulatory approaches that modify the 2'-OH group, this study explores strategic base modifications using 5-carboxylcytosine (ca5C). We developed a technique where ca5C is transformed into dihydrouracil via treatment with borane-pyridine complex or 2-picoline borane complex, leading to base mutations that directly impact RNA functionality. This innovative strategy effectively manages CRISPR-Cas9 system activities, significantly minimizing off-target effects. Our approach not only demonstrates a significant advancement in RNA manipulation but also offers a new method for the precise control of gene editing technologies, showcasing its potential for broad application in chemical biology.
与传统的修饰2'-OH基团的RNA调控方法不同，本研究探索了使用5-羧基胞嘧啶（ca5C）进行的策略性碱基修饰。我们开发了一种技术，通过用硼烷-吡啶络合物或2-甲基吡啶硼烷络合物处理，将ca5C转化为二氢尿嘧啶，从而导致直接影响RNA功能的碱基突变。这种创新策略有效地控制了CRISPR-Cas9系统的活性，显著降低了脱靶效应。我们的方法不仅展示了RNA操作方面的重大进展，还为基因编辑技术的精确控制提供了一种新方法，显示出其在化学生物学中广泛应用的潜力。
