Critical challenges and advances in recombinant adeno‐associated virus (rAAV) biomanufacturing

Gene therapy is a promising therapeutic approach for genetic and acquired diseases nowadays. Among DNA delivery vectors, recombinant adeno‐associated virus (rAAV) is one of the most effective and safest vectors used in commercial drugs and clinical trials. However, the current yield of rAAV biomanuf...

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Bibliographic Details
Published in:Biotechnology and bioengineering 2023-09, Vol.120 (9), p.2601-2621
Main Authors: Fu, Qiang, Polanco, Ashli, Lee, Yong Suk, Yoon, Seongkyu
Format: Article
Language:English
Subjects:
Biotechnology
capsid recovery
Clinical trials
continuous manufacturing
Deoxyribonucleic acid
DNA
Gene therapy
gene therapy manufacturing
Impurities
in silico modeling
inducible system
multiomics
Productivity
recombinant AAV (rAAV)
System effectiveness
Vectors
Viruses
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Summary:Gene therapy is a promising therapeutic approach for genetic and acquired diseases nowadays. Among DNA delivery vectors, recombinant adeno‐associated virus (rAAV) is one of the most effective and safest vectors used in commercial drugs and clinical trials. However, the current yield of rAAV biomanufacturing lags behind the necessary dosages for clinical and commercial use, which embodies a concentrated reflection of low productivity of rAAV from host cells, difficult scalability of the rAAV‐producing bioprocess, and high levels of impurities materialized during production. Those issues directly impact the price of gene therapy medicine in the market, limiting most patients’ access to gene therapy. In this context, the current practices and several critical challenges associated with rAAV gene therapy bioprocesses are reviewed, followed by a discussion of recent advances in rAAV‐mediated gene therapy and other therapeutic biological fields that could improve biomanufacturing if these advances are integrated effectively into the current systems. This review aims to provide the current state‐of‐the‐art technology and perspectives to enhance the productivity of rAAV while reducing impurities during production of rAAV. The current critical challenges and advances in recombinant adeno‐associated virus (rAAV) manufacturing are addressed. Multi‐omics, in‐silico models, synthetic biology/inducible system, continuous manufacturing, and advanced purification methods are discussed as future breakthroughs to overcome the current biomanufacturing challenges (low productivity, high empty/partial capsid ratio, and scalability issues).
ISSN:0006-3592
1097-0290
DOI:10.1002/bit.28412