单碱基水平上胞嘧啶碱基编辑器(CBE)的研究进展

doi:10.11843/j.issn.0366-6964.2020.01.001

摘要/Abstract

摘要： 尽管新一代基因编辑技术CRISPR/Cas9拥有众多优点，但在执行单个碱基水平的突变时其效率往往很低。由于DNA的双链断裂具有很多的不确定性，又加上基于供体模板的同源末端重组（homology directed repair，HDR）仅仅发生在分裂活跃的细胞中，而非同源末端连接（non-homologous end joining，NHEJ）在整个细胞周期中都可以发生，因此，传统CRISPR/Cas9在单碱基分辨率上进行基因编辑时存在一定弊端。碱基编辑器（base editor，BE）的出现则在一定程度上弥补了这一缺陷。胞嘧啶碱基编辑器（cytosine base editor，CBE）或腺嘌呤碱基编辑器（adenine base editor，ABE）都能够在不引起双链断裂的情况下实现C·G到T·A或A·T到G·C的转换，极大地提高了单碱基编辑的应用价值。本文侧重对出现较早的CBE的原理、发展、应用及存在的问题进行综述，以期为高效单碱基突变工具在生物医学和畜牧业生产中的应用提供有益的参考和借鉴。

关键词: 基因编辑, 单碱基突变, 胞嘧啶碱基编辑器

Abstract: Although the new generation of gene editing technology CRISPR/Cas9 has many advantages, it is often inefficient when performing mutations at a single base level. Due to the uncertainties in DNA double-strand breaks, homology directed repair (HDR) based on donor template occurs only in the actively dividing cells, however, non-homologous end joining (NHEJ) works in the whole cell cycle, therefore, it seems to be insufficient when traditional CRISPR/Cas9 performs gene editing at a single base level. The advent of the base editor (BE) has greatly relieved this dilemma. The cytosine base editor (CBE) or the adenine base editor (ABE) can both achieve C·G to T·A or A·T to G·C conversion without causing double-strand breaks, thus greatly improving the application value of single base editing. This paper focuses on the principle, development, application and existing problems of CBE, in order to provide useful reference for the application of efficient single base mutation tools in biomedical and animal husbandry production.

Key words: gene editing, single base mutation, cytosine base editor

中图分类号:

李广栋, 张鲁, 富俊才, 连正兴, 刘国世. 单碱基水平上胞嘧啶碱基编辑器(CBE)的研究进展[J]. 畜牧兽医学报, 2020, 51(1): 1-8.

LI Guangdong, ZHANG Lu, FU Juncai, LIAN Zhengxing, LIU Guoshi. Research Progress of Cytosine Base Editor at the Single Base Level[J]. Acta Veterinaria et Zootechnica Sinica, 2020, 51(1): 1-8.

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