A Novel Nucleobase Modification Strategy for Controlling RNA-Guided Nucleic Acid Cleavage  

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作  者:Huajun Lei Ruochen Fan Xiaofang Ye Wei Xiong Shuangyu Cui Tianying Zeng Tian Tian Xiang Zhou 

机构地区:[1]College of Chemistry and Molecular Sciences,Key Laboratory of Biomedical Polymers of Ministry of Education,Hubei Province Key Laboratory of Allergy and Immunology,Wuhan University,Wuhan 430072

出  处:《CCS Chemistry》2023年第12期2933-2944,共12页中国化学会会刊(英文)

基  金:the National Natural Science Foundation of China(grant nos.22177089,91853119,21721005,91753201,21877086,and 22177088);the Hubei Natural Science Foundation for Distinguished Young Scholars(grant no.2019CFA064);the Fundamental Research Funds for the Central Universities(grant no.2042019-kf0189).

摘  要:Clustered regularly interspaced short palindromic repeat(CRISPR)technologies have opened new scientific avenues widely used in biomedical research.But simple and efficient strategies to reversibly control CRISPR are lacking.In contrast to previous methods of attaching molecules to the ribose of guide RNAs(gRNAs),we focused on molecules that can directly react with nucleobases.Here,we developed a new strategy to switch off the CRISPR system by efficiently installing 4-(bromomethyl)phenylboronic acid onto nucleobases in gRNAs.CRISPR can then be activated by hydrogen peroxide(H_(2)O_(2)).Collectively,this work demonstrates boronic acid reversibly modulating CRISPR systems through a H_(2)O_(2)-responsive manner.

关 键 词:nucleobase modification guide RNA boronic acid H_(2)O_(2)responsive regulatory clustered regularly interspaced short palindromic repeat 

分 类 号:Q78[生物学—分子生物学]

 

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