C-to-A碱基编辑关键问题研究与技术开发

碱基编辑作为基因组编辑前沿技术，为合成生物学研究提供高效、精准、高通量的碱基定点替换。目前常用的胞嘧啶碱基编辑器和腺嘌呤碱基编辑器仅能实现C-to-T和A-to-G两种类型精确碱基编辑，一定程度限制该项技术的广泛应用。前期研究发现胞嘧啶碱基编辑器可以在部分野生型大肠杆菌中利用未知DNA修复系统实现C-to-A碱基编辑。本课题拟从挖掘C-to-A碱基编辑的关键修复基因出发，解析C-to-A DNA修复机理；通过C-to-A修复系统的人工设计，研究构建通用的C-to-A新型碱基编辑器，丰富碱基编辑种类，为合成生物学研究提供更完善的基因组编辑技术。

Base editing, as a cutting-edge technology of genome editing, provides efficient, accurate and high-throughput base replacement for the research of synthetic biology. However, only C to T and A to G editing could be achieved by cytosine base editor and adenine base editor now, which significantly limits the application. In our previous research, C could be edited to A in some wild type E. coli by cytosine base editor with the help of an unknown DNA repair system. In this study, the key repair genes evolved in C to A base editing will be identified, and the repair mechanism will be analyzed. Ultimately, a novel C to A base editor will be constructed for synthetic biology research by an artificial C-to-A repair system.