战略性碱基修饰修饰RNA功能，减少CRISPR-Cas9脱靶。

IF 13.1 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Nucleic Acids Research Pub Date : 2025-02-08 DOI:10.1093/nar/gkaf082

Kaisong Zhang, Wei Shen, Yunting Zhao, Xinyan Xu, Xingyu Liu, Qianqian Qi, Siqi Huang, Tian Tian, Xiang Zhou

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引用次数: 0

摘要

与传统的修饰2'-OH基团的RNA调控方法相比，本研究探索了使用5-羧基胞嘧啶（ca5C）进行战略性碱基修饰。我们开发了一种技术，将ca5C通过硼烷-吡啶络合物或2-吡啶硼烷络合物转化为二氢尿嘧啶，导致碱基突变，直接影响RNA功能。这一创新策略有效地管理CRISPR-Cas9系统活动，显著减少脱靶效应。我们的方法不仅展示了RNA操作的重大进步，而且为精确控制基因编辑技术提供了一种新的方法，展示了其在化学生物学中的广泛应用潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Strategic base modifications refine RNA function and reduce CRISPR-Cas9 off-targets.

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.

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来源期刊

Nucleic Acids Research 生物-生化与分子生物学

CiteScore

27.10

自引率

4.70%

发文量

1057

审稿时长

2 months

期刊介绍： Nucleic Acids Research (NAR) is a scientific journal that publishes research on various aspects of nucleic acids and proteins involved in nucleic acid metabolism and interactions. It covers areas such as chemistry and synthetic biology, computational biology, gene regulation, chromatin and epigenetics, genome integrity, repair and replication, genomics, molecular biology, nucleic acid enzymes, RNA, and structural biology. The journal also includes a Survey and Summary section for brief reviews. Additionally, each year, the first issue is dedicated to biological databases, and an issue in July focuses on web-based software resources for the biological community. Nucleic Acids Research is indexed by several services including Abstracts on Hygiene and Communicable Diseases, Animal Breeding Abstracts, Agricultural Engineering Abstracts, Agbiotech News and Information, BIOSIS Previews, CAB Abstracts, and EMBASE.