碱基编辑技术(base editing)是基于CRISPR/Cas系统发展起来的新型靶基因修饰技术,目前依据碱基修饰酶的不同可分为胞嘧啶碱基编辑器(cytosine base editor, CBE)和腺嘌呤碱基编辑器(adenine base editor, ABE)。这两类碱基编辑系统利用胞嘧啶脱氨酶或人工进化的腺嘌呤脱氨酶对靶位点进行精准的碱基编辑,最终可以分别实现C-T (G-A)或A-G (T-C)的碱基替换。碱基编辑技术自2016年被开发以来,因其高效、不依赖DNA双链断裂产生、无需供体DNA参与等优势,已经成功应用在各种动物、植物及其他生物中,为基因治疗及精准作物育种等领域提供了重要技术支撑。本文从碱基编辑技术的特点、开发过程、优化、应用、脱靶效应及改善策略等方面进行了系统介绍,最后对未来需要迫切解决的一些问题进行了分析和展望,以期为相关领域的科研人员进一步了解、使用及优化碱基编辑系统提供参考。

Base editing is a newly developed precise genome editing technique based on the CRISPR/Cas system. According to different base modification enzymes, the current base editing systems can be divided into cytosine base editors (CBE) and adenine base editors (ABE). They use cytosine deaminases or artificially evolved adenine deaminases to perform single-base editing, and achieve C to T (G to A) or A to G (T to C) substitutions, respectively. Due to high efficiency, independence of DNA double-strand breaks, and no need for donor DNA, base editing systems have been successfully applied in diverse species including animals, plants and other organisms since the first report in 2016. Therefore, base editing systems will have a high prospect of providing important support for gene therapy and crop genetic improvement in the future. In this review, we describe the development and current applications of base editing systems for basic research and biotechnology, highlight the challenges, and discuss the directions for future research in this important field. The information presented may facilitate interested researchers to grasp the principles of base editing, to use relevant base editing tools in their own studies, or to innovate new versions of base editing in the future.