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中国科学院广州生物医药与健康研究院赖良学研究员团队在Frontiers of Medicine发表综述论文《碱基编辑器：在生物医学中的发展与应用》(Base editors: development and applications in biomedicine）。文章回顾了碱基编辑器的发展历程，总结了其在生物医学领域如基因功能研究、疾病建模和基因治疗等方面的应用，并探讨了其在治疗应用中的未来前景与挑战。

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.

碱基编辑器（BE）是一种通过将CRISPR/Cas系统与单个脱氨酶相结合而开发的基因编辑工具，能够在活细胞中实现DNA或RNA的精确单碱基替换，且不会产生DNA双链断裂（DSB），也无需供体DNA模板。与其他传统人工核酸酶系统（如CRISPR/Cas9）相比，碱基编辑器提供了更精确和安全的基因组编辑效果，因为Cas9诱导的DSB会对基因组造成严重损伤。因此，碱基编辑器在生物医学领域具有重要应用，包括基因功能研究、定向蛋白质进化、遗传谱系追踪、疾病建模及基因治疗等方面。自两种主要的碱基编辑器——胞嘧啶碱基编辑器（CBEs）和腺嘌呤碱基编辑器（ABEs）问世以来，科学家们已开发出100 多种优化的碱基编辑器，其编辑效率、精准度、特异性、靶向范围以及体内递送能力均得到提升，极大地增强了其在生物医学中的应用潜力。本文综述了碱基编辑器的最新发展，总结了其在生物医学领域的应用，并探讨了其在治疗应用方面的未来前景与挑战。

原文信息

标题

Base editors: development and applications in biomedicine

作者

Yanhui Liang1,2,3, Fangbing Chen1,2,3,4, Kepin Wang1,2,3,4, Liangxue Lai1,2,3,4

机构

1. China-New Zealand Joint Laboratory on Biomedicine and Health, CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Centre for Regenerative Medicine and Health, Hong Kong Institute of Science and Innovation, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China

2. Research Unit of Generation of Large Animal Disease Models, Chinese Academy of Medical Sciences (2019RU015), Guangzhou 510530, China

3. Sanya Institute of Swine Resource, Hainan Provincial Research Centre of Laboratory Animals, Sanya 572000, China

4. Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, Wuyi University, Jiangmen 529020, China

通讯作者

Liangxue Lai

来源: Engineering前沿