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 safe a 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 the 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 sys tem, 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.