Simplifying the Efficient Clinical-Grade Production of Viruses:One-Size-Fits-All Transfection Reagent,From Process Development to GMP-grade Production

摘要

Initially intended for the treatment of hereditary single-gene defects, most gene therapies are also aimed at acquired diseases such as cancer, cardiovascular, and neurodegenerative pathologies. The recrudescence of viral vector-based preclinical andclinical trials is attributed to the advances made in developing new viral vector systems guided by safety, specificity, and potency considerations.While substantial efforts have been made in fine-tuning plasmid vector design to improve titer and transgene expression, one of the current bottlenecks that needs to be addressed is the transition from small-scale development toward a large-scale manufacturing process that can support potential commercial requirements. While stable viral production would at first appear to be the easiest option, there are considerable drawbacks, with respect to generation of efficient producer cell lines and maintenance of reproducible titer yields over time. Therefore, the majority of virus production is currently achieved by transient gene expression (TGE) (Merten et al., 2016).