{"title":"Strategic base modifications refine RNA function and reduce CRISPR-Cas9 off-targets.","authors":"Kaisong Zhang, Wei Shen, Yunting Zhao, Xinyan Xu, Xingyu Liu, Qianqian Qi, Siqi Huang, Tian Tian, Xiang Zhou","doi":"10.1093/nar/gkaf082","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":19471,"journal":{"name":"Nucleic Acids Research","volume":"53 4","pages":""},"PeriodicalIF":16.6000,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11833691/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nucleic Acids Research","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1093/nar/gkaf082","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
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.
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.
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