碱基编辑系统研究最新进展及应用

Recent advances and applications of base editing systems

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 (Homology directed 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 (Base editors，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。

Abstract:

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.