碱基编辑系统研究最新进展及应用  

Recent advances and applications of base editing systems

作　　者：徐鑫[1] 刘明军 Xin Xu;Mingjun Liu(College of Life Science and Technology,Xinjiang University,Urumqi 830046,Xinjiang,China;Institute of Animal Biotechnology,Xinjiang Academy of Animal Science,Urumqi 830026,Xinjiang,China)

机构地区：[1]新疆大学生命科学与技术学院,新疆乌鲁木齐830046 [2]新疆畜牧科学院生物技术研究所,新疆乌鲁木齐830026

出　　处：《生物工程学报》2021年第7期2307-2321,共15页Chinese Journal of Biotechnology

基　　金：转基因生物新品种培育重大专项(No.2014ZX08010-004)资助。

摘　　要：CRISPR系统能够在基因组DNA中完成精准编辑,但依赖于细胞内的同源重组(Homologydirected recombination,HDR)修复途径,且效率极低。基于CRISPR/Cas9系统开发的碱基编辑技术(Base editing)通过将失去切割活性的核酸酶与不同碱基脱氨基酶融合,构建了两套碱基编辑系统(Baseeditors,BE):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)。这两类编辑器分别能够在不产生DNA双链断裂的前提下在基因靶位点完成C>T (G>A)或A>G (T>C)的替换,最终实现精准的碱基编辑。目前碱基编辑技术已经广泛应用于基因治疗、动物模型构建、精准动物育种和基因功能分析等领域,为基础和应用研究提供了强大的技术工具。文中概括了碱基编辑技术的研发过程、技术优势、应用现状、存在问题及改进策略,以期为相关领域的科研人员了解和使用碱基编辑系统提供参考。The CRISPR system is able to accomplish precise base editing in genomic DNA, but relies on the cellular homology-directed recombination repair pathway and is therefore extremely inefficient. Base editing is a new genome editing technique developed based on the CRISPR/Cas9 system. Two base editors(cytosine base editor and adenine base editor) were developed by fusing catalytically disabled nucleases with different necleobase deaminases. These two base editors are able to perform C>T(G>A) or A>G(T>C) transition without generating DNA double-stranded breaks. The base editing technique has been widely used in gene therapy, animal models construction, precision animal breeding and gene function analysis, providing a powerful tool for basic and applied research. This review summarized the development process, technical advantages, current applications, challenges and perspectives for base editing technique, aiming to help the readers better understand and use the base editing technique.

关 键 词：CRISPR/Cas9 碱基编辑 胞嘧啶碱基编辑器 腺嘌呤碱基编辑器 

分 类 号：Q789[生物学—分子生物学]