Photo-Modulation of Gene-Editing Enzymes CRISPR/Cas9 with Bifunctional Small-Molecule Ligands

doi:10.1002/cjoc.202300452

	Photo-Modulation of Gene-Editing Enzymes CRISPR/Cas9 with Bifunctional Small-Molecule Ligands
	Zhang, Yidan 1,2; Zhang, Yixin 1; Han, Lili1,3 ; Che, Qiaoling1,3 ; Tan, Jiawei 1; Zou, Peng 1; Chen, Yiyun1,2,3
	2023-10-01
发表期刊	CHINESE JOURNAL OF CHEMISTRY (IF:5.5[JCR-2023],5.2[5-Year])
ISSN	1001-604X
EISSN	1614-7065
发表状态	已发表
DOI	10.1002/cjoc.202300452
摘要	The control of protein functions with light is valuable for spatiotemporal probing of biological systems. Current small-molecule photo- modulation methods include the light-induced uncaging of inhibitors and chromophore-assisted light inactivation with reactive oxygen species (ROS). However, the constant target protein expression results in inadequate photo-modulation efficiency, particularly for less potent inhibitors and chromophores. Herein, we report a novel bifunctional small-molecule ligands strategy to photo-modulate gene-editing enzymes CRISPR/Cas9. A coumarin-derived small-molecule ligand Bhc-BRD0539 is developed to uncage the active inhibitor upon light irradiation and to generate ROS in the Cas9 proximity for the dual inhibition of Cas9 activity. Our results highlight the synergistic photo-modulation with bifunctional small-molecule ligands, which offers a valuable addition to current CRISPR/Cas9 photo-modulation technologies and may extend to other protein classes.
关键词	Gene-editing Small-molecule ligands Enzyme modulation DNA cleavage Photoswitch Inhibitors
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收录类别	SCI
语种	英语
资助项目	This work is supported by the National Natural Science Foundation of China (22337005, 22277133, 91753126), the Youth Innovation Promotion Association (CAS 2023266), the CAS Interdisciplinary Innovation Team (JCTD-2020-16), the Program of Shanghai Academic/[
WOS研究方向	Chemistry
WOS类目	Chemistry, Multidisciplinary
WOS记录号	WOS:001079583500001
出版者	WILEY-V C H VERLAG GMBH
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/343605
专题	物质科学与技术学院物质科学与技术学院_特聘教授组_陈以昀组物质科学与技术学院_博士生
通讯作者	Chen, Yiyun
作者单位	1.Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Organ Chem, State Key Lab Chem Biol, 345 Lingling Rd, Shanghai 200032, Peoples R China 2.Univ Chinese Acad Sci, Sch Chem & Mat Sci, Hangzhou Inst Adv Study, 1 Sub Lane Xiangshan, Hangzhou 310024, Zhejiang, Peoples R China 3.ShanghaiTech Univ, Sch Phys Sci & Technol, 100 Haike Rd, Shanghai 201210, Peoples R China
通讯作者单位	物质科学与技术学院
推荐引用方式 GB/T 7714	Zhang, Yidan,Zhang, Yixin,Han, Lili,et al. Photo-Modulation of Gene-Editing Enzymes CRISPR/Cas9 with Bifunctional Small-Molecule Ligands[J]. CHINESE JOURNAL OF CHEMISTRY,2023.
APA	Zhang, Yidan.,Zhang, Yixin.,Han, Lili.,Che, Qiaoling.,Tan, Jiawei.,...&Chen, Yiyun.(2023).Photo-Modulation of Gene-Editing Enzymes CRISPR/Cas9 with Bifunctional Small-Molecule Ligands.CHINESE JOURNAL OF CHEMISTRY.
MLA	Zhang, Yidan,et al."Photo-Modulation of Gene-Editing Enzymes CRISPR/Cas9 with Bifunctional Small-Molecule Ligands".CHINESE JOURNAL OF CHEMISTRY (2023).