重组腺相关病毒载体转导与整合机制的研究进展  

Research progress on the transduction and integration mechanisms of recombinant adeno-associated virus vectors

作　　者：何伟伟 郑明岚 陈建军 周长慧 常艳 HE Weiwei;ZHENG Minglan;CHEN Jianjun;ZHOU Changhui;CHANG Yan(China State Institute of Pharmaceutical Industry,Shanghai 201203,China;Shanghai Innostar Bio-tech Co.Ltd,Shanghai 201203,China;Yangtze River Delta Sub-Center for Drug Evaluation and Inspection,National Medical Products Administration,Shanghai 201203,China)

机构地区：[1]中国医药工业研究总院,上海201203 [2]上海益诺思生物技术股份有限公司,上海201203 [3]国家药品监督管理局药品审评检查长三角分中心,上海201203

出　　处：《世界临床药物》2024年第4期435-439,共5页World Clinical Drug

基　　金：上海市科委研发公共服务平台项目(21DZ2291000)。

摘　　要：重组腺相关病毒载体因整合率、致病性低等优势,被广泛应用为基因治疗产品的递送载体,但可能在宿主基因组中发生整合,有潜在遗传毒性风险。因此,需要对重组腺相关病毒载体的转导过程和基因组整合机制进行深入研究,以建立适用且高效的遗传毒性评价方法。该文对重组腺相关病毒载体的生物学特性进行简介,对其转导过程、可能的整合机制、整合位点的偏好以及潜在的遗传毒性风险进行综述,并对重组腺相关病毒载体的遗传毒性评价方法作一展望,以期为进一步评价重组腺相关病毒载体的遗传毒性风险提供参考。Recombinant adeno-associated virus vectors are widely used as delivery vectors for gene therapy products due to their low integration rate and low pathogenicity.But,they can still be integrated in the host genome,resulting in potential genotoxicity risks.So,it is necessary to conduct in-depth research on the transduction process and genome integration mechanism of recombinant adeno-associated virus vectors,in order to establish an appropriate and efficient genotoxicity evaluation method.This paper introduced the biological characteristics of recombinant adeno-associated virus vectors,reviewed the transduction process,possible integration mechanisms,integration site preferences and potential genotoxicity risks,and prospected the genotoxicity evaluation methods of recombinant adeno-associated virus vectors,to provide a reference for further evaluation of the genotoxicity risk of recombinant adeno-associated virus vectors.

关 键 词：重组腺相关病毒 载体 转导 整合机制 遗传毒性 

分 类 号：R450[医药卫生—治疗学]