A far-red light–inducible CRISPR-Cas12a platform for remote-controlled genome editing and gene activation

Xinyi Wang; Kaili Dong; Deqiang Kong; Yang Zhou; Jianli Yin; Fengfeng Cai; Meiyan Wang; Haifeng Ye

doi:10.1126/sciadv.abh2358

A far-red light–inducible CRISPR-Cas12a platform for remote-controlled genome editing and gene activation

Xinyi Wang, Kaili Dong, Deqiang Kong, Yang Zhou, Jianli Yin, Fengfeng Cai, Meiyan Wang, Haifeng Ye

School of Life Sciences

Research output: Contribution to journal › Article › peer-review

37 Scopus citations

Abstract

The CRISPR-Cas12a has been harnessed as a powerful tool for manipulating targeted gene expression. The possibility to manipulate the activity of CRISPR-Cas12a with a more precise spatiotemporal resolution and deep tissue permeability will enable targeted genome engineering and deepen our understanding of the gene functions underlying complex cellular behaviors. However, currently available inducible CRISPR-Cas12a systems are limited by diffusion, cytotoxicity, and poor tissue permeability. Here, we developed a far-red light (FRL)–inducible CRISPRCas12a (FICA) system that can robustly induce gene editing in mammalian cells, and an FRL-inducible CRISPR-dCas12a (FIdCA) system based on the protein-tagging system SUperNova (SunTag) that can be used for gene activation under light-emitting diode–based FRL. Moreover, we show that the FIdCA system can be deployed to activate target genes in mouse livers. These results demonstrate that these systems developed here provide robust and efficient platforms for programmable genome manipulation in a noninvasive and spatiotemporal fashion.

Original language	English
Article number	, eabh2358
Journal	Science Advances
Volume	7
Issue number	50
DOIs	https://doi.org/10.1126/sciadv.abh2358
State	Published - Dec 2021

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title = "A far-red light–inducible CRISPR-Cas12a platform for remote-controlled genome editing and gene activation",

abstract = "The CRISPR-Cas12a has been harnessed as a powerful tool for manipulating targeted gene expression. The possibility to manipulate the activity of CRISPR-Cas12a with a more precise spatiotemporal resolution and deep tissue permeability will enable targeted genome engineering and deepen our understanding of the gene functions underlying complex cellular behaviors. However, currently available inducible CRISPR-Cas12a systems are limited by diffusion, cytotoxicity, and poor tissue permeability. Here, we developed a far-red light (FRL)–inducible CRISPRCas12a (FICA) system that can robustly induce gene editing in mammalian cells, and an FRL-inducible CRISPR-dCas12a (FIdCA) system based on the protein-tagging system SUperNova (SunTag) that can be used for gene activation under light-emitting diode–based FRL. Moreover, we show that the FIdCA system can be deployed to activate target genes in mouse livers. These results demonstrate that these systems developed here provide robust and efficient platforms for programmable genome manipulation in a noninvasive and spatiotemporal fashion.",

author = "Xinyi Wang and Kaili Dong and Deqiang Kong and Yang Zhou and Jianli Yin and Fengfeng Cai and Meiyan Wang and Haifeng Ye",

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AU - Wang, Xinyi

AU - Dong, Kaili

AU - Kong, Deqiang

AU - Zhou, Yang

AU - Yin, Jianli

AU - Cai, Fengfeng

AU - Wang, Meiyan

AU - Ye, Haifeng

PY - 2021/12

Y1 - 2021/12

N2 - The CRISPR-Cas12a has been harnessed as a powerful tool for manipulating targeted gene expression. The possibility to manipulate the activity of CRISPR-Cas12a with a more precise spatiotemporal resolution and deep tissue permeability will enable targeted genome engineering and deepen our understanding of the gene functions underlying complex cellular behaviors. However, currently available inducible CRISPR-Cas12a systems are limited by diffusion, cytotoxicity, and poor tissue permeability. Here, we developed a far-red light (FRL)–inducible CRISPRCas12a (FICA) system that can robustly induce gene editing in mammalian cells, and an FRL-inducible CRISPR-dCas12a (FIdCA) system based on the protein-tagging system SUperNova (SunTag) that can be used for gene activation under light-emitting diode–based FRL. Moreover, we show that the FIdCA system can be deployed to activate target genes in mouse livers. These results demonstrate that these systems developed here provide robust and efficient platforms for programmable genome manipulation in a noninvasive and spatiotemporal fashion.

AB - The CRISPR-Cas12a has been harnessed as a powerful tool for manipulating targeted gene expression. The possibility to manipulate the activity of CRISPR-Cas12a with a more precise spatiotemporal resolution and deep tissue permeability will enable targeted genome engineering and deepen our understanding of the gene functions underlying complex cellular behaviors. However, currently available inducible CRISPR-Cas12a systems are limited by diffusion, cytotoxicity, and poor tissue permeability. Here, we developed a far-red light (FRL)–inducible CRISPRCas12a (FICA) system that can robustly induce gene editing in mammalian cells, and an FRL-inducible CRISPR-dCas12a (FIdCA) system based on the protein-tagging system SUperNova (SunTag) that can be used for gene activation under light-emitting diode–based FRL. Moreover, we show that the FIdCA system can be deployed to activate target genes in mouse livers. These results demonstrate that these systems developed here provide robust and efficient platforms for programmable genome manipulation in a noninvasive and spatiotemporal fashion.

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A far-red light–inducible CRISPR-Cas12a platform for remote-controlled genome editing and gene activation

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