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

  • Review
  • Virology
  • Published:
Chinese Science Bulletin

Abstract

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 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.

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Acknowledgments

The authors thank Fathe Kristin (PhD, Department of Chemistry and Biochemistry, College of Natural Science, University of Texas at Austin) for her help in writing the manuscript and critical review. This work was supported by the National Natural Science Foundation of China (81071850 and 81301307).

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Authors and Affiliations

  1. Laboratory of Viral and Gene Therapy, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, 200438, China

    Zenghui Xu, Chuanyin Shi & Qijun Qian

  2. Department of Biotherapy, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, 200438, China

    Qijun Qian

  3. Xinyuan Institute of Medicine and Biotechnology, College of Life Science, Zhejiang Sci-Tech University, Hangzhou, 310018, China

    Qijun Qian

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  1. Zenghui Xu
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  2. Chuanyin Shi
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Correspondence to Qijun Qian.

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Xu, Z., Shi, C. & Qian, Q. Scalable manufacturing methodologies for improving adeno-associated virus-based pharmaprojects. Chin. Sci. Bull. 59, 1845–1855 (2014). https://doi.org/10.1007/s11434-014-0197-6

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