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

IF 6.6 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell Chemical Biology Pub Date : 2024-10-17 DOI:10.1016/j.chembiol.2024.09.006

Qianqian Qi , Xingyu Liu , Wei Xiong , Kaisong Zhang , Wei Shen , Yuanyuan Zhang , Xinyan Xu , Cheng Zhong , Yan Zhang , Tian Tian , Xiang Zhou

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Abstract

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.

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通过光控化学修饰引导 RNA 减少 CRISPR-Cas9 的脱靶效应

本文介绍了一种光催化点击化学方法，与传统的 RNA 功能调节方法相比，这种方法具有重大进步。这种创新方法利用光激活的小分子，提供了高水平的 RNA 调节精度和控制能力，在复杂的细胞过程中尤其有效。通过将这种策略应用于 CRISPR-Cas9 基因编辑，我们证明了它在增强基因编辑特异性和显著减少脱靶效应方面的有效性。我们的方法在 RNA 中采用乙烯基醚修饰，在可见光下用菲醌衍生物激活，形成一个 CRISPR-OFF 开关，精确调节 CRISPR 系统的活性。这种方法不仅代表了基因组干预技术的进步，而且在基因调控方面具有广泛的应用前景，为在治疗基因组学中进行更安全、更可靠的基因编辑铺平了道路。

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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来源期刊

Cell Chemical Biology Biochemistry, Genetics and Molecular Biology-Molecular Medicine

CiteScore

14.70

自引率

2.30%

发文量

143

期刊介绍： Cell Chemical Biology, a Cell Press journal established in 1994 as Chemistry & Biology, focuses on publishing crucial advances in chemical biology research with broad appeal to our diverse community, spanning basic scientists to clinicians. Pioneering investigations at the chemistry-biology interface, the journal fosters collaboration between these disciplines. We encourage submissions providing significant conceptual advancements of broad interest across chemical, biological, clinical, and related fields. Particularly sought are articles utilizing chemical tools to perturb, visualize, and measure biological systems, offering unique insights into molecular mechanisms, disease biology, and therapeutics.