Scalable manufacturing methodologies for improving adeno-associated virus-based pharmaprojects  

作　　者：Zenghui Xu Chuanyin Shi Qijun Qian 

机构地区：[1]Laboratory of Viral and Gene Therapy,Eastern Hepatobiliary Surgery Hospital,The Second Military Medical University [2]Department of Biotherapy,Eastern Hepatobiliary Surgery Hospital,The Second Military Medical University [3]Xinyuan Institute of Medicine and Biotechnology,College of Life Science,Zhejiang Sci-Tech University

出　　处：《Chinese Science Bulletin》2014年第16期1845-1855,共11页

基　　金：supported by the National Natural Science Foundation of China (81071850 and 81301307)

摘　　要：Adeno-associated virus(AAV)is a promising viral vector and meets most requirements of being a safe biological agent.However,the commercialization of AAV has been hampered due to the limitation of large-scale production,and only a small number of clinical trials have been launched.In recent years,progresses in scalable manufacturing of AAV have dramatically improved AAVbased clinical researches,and have assisted the development of investigational drug products.An AAV1-based investigational product,Glybera,has been formally approved by European Commission for the treatment of lipoprotein lipase deficiency(LPLD).Glybera was the first gene therapy product in the western world,and the production process involves a scalable baculovirus-insect cell system.However,many problems still need to be solved to improve the productivity and quality of AAV.The present review gives critical insights into current state-of-the-art scalable producing methodologies of AAV,such as baculovirus-insect cell system,HSV complementation system,and Ad complementation system,along with a discussion on the problems,solutions,and developmental trends.Novel AAV-producing platforms in Saccharomyces cerevisiae and vaccinia virus complementation system will also be discussed.Adeno-associated virus （AAV） is a promising viral vector and meets most requirements of being a safe biological agent. However, the commercialization of AAV has been hampered due to the limitation of large-scale production, and only a small number of clinical trials have been launched. In recent years, progresses in scalable manufacturing of AAV have dramatically improved AAV- based clinical researches, and have assisted the develop- ment of investigational drug products. An AAVl-based investigational product, Glybera, has been formally approved by European Commission for the treatment of lipoprotein lipase deficiency （LPLD）. Glybera was the first gene therapy product in the western world, and the pro- duction process involves a scalable baculovirus-insect cell system. However, many problems still need to be solved to improve the productivity and quality of AAV. The present review gives critical insights into current state-of-the-art scalable producing methodologies of AAV, such as bacu-lovirus-insect cell system, HSV complementation system, and Ad complementation system, along with a discussion on the problems, solutions, and developmental trends.Novel AAV-producing platforms in Saccharomyces cere- visiae and vaccinia virus complementation system will also be discussed.

关 键 词：腺相关病毒 制造方法 基础 可伸缩 临床试验 基因治疗 昆虫细胞 大规模生产 

分 类 号：R373[医药卫生—病原生物学]