重组腺相关病毒载体生产用质粒的设计与合规考量  

Considerations for the Plasmid Designing and Compliance of Recombinant Adeno-associated Virus Vector Production

作　　者：陈一飞 马琳莎 刘芬 CHEN Yifei;MA Linsha;LIU Fen(Shanghai Center for Drug Evaluation and Inspection,Shanghai 201203;South China Agricultural University,Guangzhou 510642)

机构地区：[1]上海药品审评核查中心,上海201203 [2]华南农业大学,广东广州510642

出　　处：《中国医药工业杂志》2024年第8期1136-1142,共7页Chinese Journal of Pharmaceuticals

摘　　要：重组腺相关病毒是当前体内基因治疗产品中最常用的载体。在其生产中,质粒是重要的起始原材料。质粒的设计与管理直接决定了产品的生物学作用机制、药学性质、有效性与安全性。因此,对质粒及其基因元件性质的理解是该类产品“质量源于设计”的管理基础。文章以商业化生产中常用的三质粒系统为例,概述了不同质粒的作用,介绍了主要基因元件,分析了质粒的设计要点,综述了合规要求,讨论了质粒的设计与合规考量,以期为以重组腺相关病毒为代表的基因治疗产品的开发和管理提供参考。At present,recombinant adeno-associated virus is the most commonly used vectors for in vivo gene therapy products.For producing virus vectors,plasmids are believed to be the important starting raw material.The designing and managing of plasmids directly contribute to the biological mechanisms,pharmaceutical properties,efficacy,and safety of products.Therefore,understanding the properties of plasmids and their gene elements is the basis for the“quality by design”of such products.The functions of different plasmids are introduced in this paper,the construction of main genetic elements are summarized,the considerations for designing of plasmids are discussed,the compliance for developing and manufacturing of plasmids are reviewed,in order to provide some references for the development and management of gene therapy products,especially for the recombinant adeno-associated virus products.

关 键 词：基因治疗产品 重组腺相关病毒载体 质粒 设计 合规 

分 类 号：R95[医药卫生—药学]