Photo-Modulation of Gene-Editing Enzymes CRISPR/Cas9 with Bifunctional Small-Molecule Ligands†
Yidan Zhang
State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032 China
School of Chemistry and Material Sciences, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, 1 Sub-lane Xiangshan, Hangzhou, Zhejiang, 310024 China
‡These authors contributed equally to this work.
Search for more papers by this authorYixin Zhang
State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032 China
‡These authors contributed equally to this work.
Search for more papers by this authorLili Han
State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032 China
School of Physical Science and Technology, ShanghaiTech University, 100 Haike Road, Shanghai, 201210 China
‡These authors contributed equally to this work.
Search for more papers by this authorQiaoling Che
State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032 China
School of Physical Science and Technology, ShanghaiTech University, 100 Haike Road, Shanghai, 201210 China
Search for more papers by this authorJiawei Tan
State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032 China
Search for more papers by this authorPeng Zou
State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032 China
Search for more papers by this authorCorresponding Author
Yiyun Chen
State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032 China
School of Chemistry and Material Sciences, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, 1 Sub-lane Xiangshan, Hangzhou, Zhejiang, 310024 China
School of Physical Science and Technology, ShanghaiTech University, 100 Haike Road, Shanghai, 201210 China
E-mail: [email protected]Search for more papers by this authorYidan Zhang
State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032 China
School of Chemistry and Material Sciences, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, 1 Sub-lane Xiangshan, Hangzhou, Zhejiang, 310024 China
‡These authors contributed equally to this work.
Search for more papers by this authorYixin Zhang
State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032 China
‡These authors contributed equally to this work.
Search for more papers by this authorLili Han
State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032 China
School of Physical Science and Technology, ShanghaiTech University, 100 Haike Road, Shanghai, 201210 China
‡These authors contributed equally to this work.
Search for more papers by this authorQiaoling Che
State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032 China
School of Physical Science and Technology, ShanghaiTech University, 100 Haike Road, Shanghai, 201210 China
Search for more papers by this authorJiawei Tan
State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032 China
Search for more papers by this authorPeng Zou
State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032 China
Search for more papers by this authorCorresponding Author
Yiyun Chen
State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032 China
School of Chemistry and Material Sciences, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, 1 Sub-lane Xiangshan, Hangzhou, Zhejiang, 310024 China
School of Physical Science and Technology, ShanghaiTech University, 100 Haike Road, Shanghai, 201210 China
E-mail: [email protected]Search for more papers by this authorDedicated to the Memory of Professor Xiyan Lu.
Comprehensive Summary
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.
Supporting Information
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Appendix S1: Supporting Information |
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