Design and Engineering of Light‐Induced Base Editors Facilitating Genome Editing with Enhanced Fidelity

Author:

Sun Yangning12,Chen Qi12,Cheng Yanbing12,Wang Xi12,Deng Zixin12,Zhou Fuling1,Sun Yuhui12ORCID

Affiliation:

1. Department of Hematology Zhongnan Hospital of Wuhan University School of Pharmaceutical Sciences Wuhan University Wuhan 430071 China

2. Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Ministry of Education) Wuhan University Wuhan 430071 China

Abstract

AbstractBase editors, which enable targeted locus nucleotide conversion in genomic DNA without double‐stranded breaks, have been engineered as powerful tools for biotechnological and clinical applications. However, the application of base editors is limited by their off‐target effects. Continuously expressed deaminases used for gene editing may lead to unwanted base alterations at unpredictable genomic locations. In the present study, blue‐light‐activated base editors (BLBEs) are engineered based on the distinct photoswitches magnets that can switch from a monomer to dimerization state in response to blue light. By fusing the N‐ and C‐termini of split DNA deaminases with photoswitches Magnets, efficient A‐to‐G and C‐to‐T base editing is achieved in response to blue light in prokaryotic and eukaryotic cells. Furthermore, the results showed that BLBEs can realize precise blue light‐induced gene editing across broad genomic loci with low off‐target activity at the DNA‐ and RNA‐level. Collectively, these findings suggest that the optogenetic utilization of base editing and optical base editors may provide powerful tools to promote the development of optogenetic genome engineering.

Funder

National Key Research and Development Program of China

National Natural Science Foundation of China

Publisher

Wiley

Subject

General Physics and Astronomy,General Engineering,Biochemistry, Genetics and Molecular Biology (miscellaneous),General Materials Science,General Chemical Engineering,Medicine (miscellaneous)

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