Critical challenges and advances in recombinant adeno-associated virus (rAAV) biomanufacturing.
Qiang FuAshli PolancoYong Suk LeeSeongkyu YoonPublished in: Biotechnology and bioengineering (2023)
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.
Keyphrases
- gene therapy
- clinical trial
- end stage renal disease
- healthcare
- primary care
- climate change
- cell free
- chronic kidney disease
- ejection fraction
- randomized controlled trial
- peritoneal dialysis
- genome wide
- induced apoptosis
- circulating tumor
- copy number
- oxidative stress
- open label
- cell proliferation
- cell cycle arrest
- patient reported
- endoplasmic reticulum stress