DNA碱基编辑器在微生物中的研究进展  

Research progress of DNA base editors in microorganisms

作　　者：刘振权 董会娜[2] 丛丽娜[1] 张大伟[2] LIU Zhenquan;DONG Huina;CONG Lina;ZHANG Dawei(School of Biological Engineering, Dalian Polytechnic University, Dalian 116034;Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308)

机构地区：[1]大连工业大学生物工程学院,辽宁大连116034 [2]中国科学院天津工业生物技术研究所,天津300308

出　　处：《工业微生物》2020年第6期41-47,共7页Industrial Microbiology

基　　金：国家重点研发计划(2018YFA0900300);国家自然科学基金项目(31800086)。

摘　　要：在众多生物中利用具有切割作用的CRISPR/Cas9系统与非同源性末端连接(non-homologous end joining,NHEJ)修复系统或同源性末端连接(homology-directed repair,HDR)修复系统共同完成基因编辑工作都有报道。但是由于NHEJ的不精确性以及一些微生物中HDR效率较低导致生物体死亡限制了该工具的发展。基于CRISPR/dCas9系统构建而成的DNA碱基编辑器作为一种编辑工具,可靶向地实现碱基之间的转换,且不导致微生物死亡。DNA碱基编辑器在微生物中已经实现靶向编辑工作,可以同时多个位点进行编辑,同时可以利用该工具将编码氨基酸的密码子转化为终止密码子,提前终止翻译过程实现对基因的失活。本文主要对DNA碱基编辑器的作用原理,发展历程以及在微生物中的应用做了概述,最后提出了该工具存在的一些不足之处,并结合相关研究展望了未来的研究方向。为在微生物中开发与利用DNA碱基编辑的研究提供了思路。The use of CRISPR/Cas9 system with its cutting function in combination with non-homologous end joining(NHEJ)or homology-directed repair(HDR)system for gene editing were reported in many organisms.However,the inaccuracy of NHEJ and the low efficiency of HDR in some microorganisms limited the development of the tools.The DNA base editors based on the CRISPR/dCas9 system could be used as an editing tool to achieve targeted conversion between bases without causing microbial death.DNA base editors had realized targeted editing in microorganisms,which could edit multiple sites at the same time.Meanwhile,the tool could be used to convert the codons encoding amino acids into stop codons,and to terminate the translation process in advance to achieve gene inactivation.In this paper,the working principle,development process and application of DNA base editors in microorganisms were summarized.Finally,some shortcomings of the tools were pointed out and the future research direction was prospected.It would provide an idea for the development and utilization of DNA base editing in microorganisms.

关 键 词：胞嘧啶碱基编辑器 腺嘌呤碱基编辑器 CRISPR/dCas9 微生物 

分 类 号：TP3[自动化与计算机技术—计算机科学与技术]