Near-infrared light activatable chemically induced CRISPR system

Lei Zhang; Xuejun Zhang; Le Qiu; Song Mao; Jia Sheng; Liming Chen; Umar Khan; Paul K. Upputuri; Yuri N. Zakharov; Mark F. Coughlan; Lev T. Perelman

doi:10.1038/s41377-025-01917-8

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Near-infrared light activatable chemically induced CRISPR system

Original Articles

- Near-infrared light activatable chemically induced CRISPR system
- Light: Science & Applications Vol. 14, Issue 9, Pages: 2433-2444(2025)
- Affiliations：
  
  1.Center for Advanced Biomedical Imaging and Photonics, Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA
  2.The RNA Institute, Department of Chemistry, University at Albany, Albany, NY, USA
- Author bio：
  
  Lei Zhang (lzhang11@bidmc.harvard.edu)
  Jia Sheng (jsheng@albany.edu)
  Lev T. Perelman (ltperel@bidmc.harvard.edu)
- Funds：
- DOI：10.1038/s41377-025-01917-8
  CLC：
- Received：31 December 2024，
  
  Revised：2025-05-27，
  
  Accepted：05 June 2025，
  
  Published Online：01 July 2025，
  
  Published：30 September 2025
- Accepted：
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Zhang, L. et al. Near-infrared light activatable chemically induced CRISPR system. Light: Science & Applications, 14, 2433-2444 (2025).
DOI：

Zhang, L. et al. Near-infrared light activatable chemically induced CRISPR system. Light: Science & Applications, 14, 2433-2444 (2025). DOI： 10.1038/s41377-025-01917-8.

摘要

Abstract

The biggest challenge in using CRISPR technologies

which limits their widespread application in medicine

is off-target effects. These effects could

in principle

be minimized by ensuring that CRISPR is activated primarily in the targeted cells

thereby reducing the likelihood of unintended genetic modifications in non-target tissues. Therefore

the development of a light activatable CRISPR approach to dynamically control gene activation in both space and time would be highly beneficial. A drawback is that the overwhelming majority of recently introduced light activatable CRISPR systems require UV or blue light exposure

severely limiting the penetration depth of light in tissue at which CRISPR can be activated

and

in the case of UV light

raising safety concerns. A small number of systems that activate CRISPR using longer wavelengths are hindered by either slow light activation or issues related to toxicity and biocompatibility of the proposed techniques in humans. To address this

we developed a split-Cas9/dCas9 system in which activation is achieved through a near-infrared photocleavable dimerization complex. This photoactivation method can be safely used in humans in vivo

easily adapted to different split-Cas9/dCas9 systems

and enables rapid

spatially precise light activation across various cell types.

关键词

Keywords

references

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