Reducing CRISPR-Cas9 off-target effects by optically controlled chemical modifications of guide RNA

被引：8

作者：

Qi, Qianqian ^{[1
]}

Liu, Xingyu ^{[1
]}

Xiong, Wei ^{[1
]}

Zhang, Kaisong ^{[1
]}

Shen, Wei ^{[1
]}

Zhang, Yuanyuan ^{[1
]}

Xu, Xinyan ^{[1
]}

Zhong, Cheng ^{[1
]}

Zhang, Yan ^{[2
]}

Tian, Tian ^{[1
]}

Zhou, Xiang ^{[1
]}

机构：

[1] Wuhan Univ, Coll Chem & Mol Sci, Key Lab Biomed Polymers,Inst Mol Med, Minist Educ,Hubei Prov Key Lab Allergy & Immunol, Wuhan 430072, Hubei, Peoples R China

[2] Nanjing Univ, Chem & Biomed Innovat Ctr ChemBIC, Sch Chem & Chem Engn, State Key Lab Analyt Chem Life Sci, Nanjing 210023, Peoples R China

来源：

CELL CHEMICAL BIOLOGY | 2024年 / 31卷 / 10期

基金：

中国国家自然科学基金;

关键词：

PHOTOCLICK CHEMISTRY; PLATFORM; SYSTEM;

D O I：

10.1016/j.chembiol.2024.09.006

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1839 / 1851.e8

页数：22

共 55 条

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