Base editors: development and applications in biomedicine

Abstract

Base editor (BE) is a gene-editing tool developed by combining the CRISPR/Cas system with an individual deaminase, enabling precise single-base substitution in DNA or RNA without generating a DNA double-strand break (DSB) or requiring donor DNA templates in living cells. Base editors offer more precise and secure genome-editing effects than other conventional artificial nuclease systems, such as CRISPR/Cas9, as the DSB induced by Cas9 will cause severe damage to the genome. Thus, base editors have important applications in the field of biomedicine, including gene function investigation, directed protein evolution, genetic lineage tracing, disease modeling, and gene therapy. Since the development of the two main base editors, cytosine base editors (CBEs) and adenine base editors (ABEs), scientists have developed more than 100 optimized base editors with improved editing efficiency, precision, specificity, targeting scope, and capacity to be delivered in vivo, greatly enhancing their application potential in biomedicine. Here, we review the recent development of base editors, summarize their applications in the biomedical field, and discuss future perspectives and challenges for therapeutic applications.

Keywords

base editing / CBE / ABE / ADAR / DdCBE / disease model / therapeutic application

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Acknowledgements

This work was financially supported by National Natural Science Foundation of China (No. 32100410); National Key Research and Development Program of China (No. 2022YFA1105403); Science and Technology Program of Guangzhou (Nos. 202201010409 and 2023A04J0732); Major Science and Technology Project of Hainan Province (No. ZDKJ2021030); 2020 Research Program of Sanya Yazhou Bay Science and Technology City (No. 202002011); Science and Technology Planning Project of Guangdong Province, China (Nos. 2020B1212060052 and 2021B1212040016); Research Unit of Generation of Large Animal Disease Models, Chinese Academy of Medical Sciences (No. 2019-I2M-5-025).

Compliance with ethics guidelines

Yanhui Liang, Fangbing Chen, Kepin Wang, and Liangxue Lai declare that they have no conflict of interest. This manuscript is a review article and does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee.

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