基于非病毒方法的大片段外源DNA定点整合技术研究进展  

Progress of Site-specific Integration of Large Exogenous DNA Fragments Based on Non-viral Methods

作　　者：崔佳 刘振华 CUI Jia;LIU Zhenhua(Lab.of Infection and Immunity,Institute of Basic Medicine,Dept.of Basic Medical,Changzhi Medical College,Changzhi 046099)

机构地区：[1]长治医学院基础医学部,基础医学研究所感染与免疫实验室,山西长治046099

出　　处：《中国医药工业杂志》2024年第8期1045-1052,共8页Chinese Journal of Pharmaceuticals

基　　金：山西省基础研究计划(自由探索类)项目(20210302124230);长治医学院博士科研启动基金项目(BS202002、BS202121)。

摘　　要：基于非病毒方法的大片段DNA定点整合技术具有成本低、容量大、无免疫原性,以及可避免遗传毒性和癌基因表达等优点,在基因治疗、细胞治疗等领域应用广泛。根据作用机制,可将基于非病毒方法的DNA定点整合技术分为3种,即基于DNA损伤修复的、基于重组酶的和基于转座酶的。3种基于非病毒方法的DNA定点整合技术均可以与成簇规律间隔短回文重复序列(CRISPR)及其相关蛋白9(Cas9)技术结合,快速、方便地将外源DNA引导至目标DNA区域。该文总结了3种基于非病毒方法的DNA定点整合技术的研究进展及其应用,以期为开发更高效的细胞治疗体系提供新思路。Site-specific integration of large DNA fragments based on non-viral methods are widely used in gene therapy and cell therapy because of their low cost,large capacity,non-immunogenicity,and the ability to avoid genotoxicity and oncogene expression.According to the mechanism,non-viral methods can be classified into three types,DNA damage repair-,recombinase-and transposase-based site-specific integration technologies.All three non-viral DNA targeting methods can be combined with the clustered regularly interspaced short palindromic repeats(CRISPR)and CRISPR associated proteins 9(Cas9)technology to quickly and easily direct exogenous DNA to the target DNA region.In this study,the research progress of the three non-viral-based DNA targeting methods and their applications are summarized to provide new ideas for the development of more efficient cell therapy systems.

关 键 词：定点整合 非病毒 CRISPR/Cas9 DNA损伤修复 重组酶/整合酶 转座酶 研究进展 

分 类 号：Q784[生物学—分子生物学]