Large-scale adeno-associated viral vector production using a herpesvirus-based system enables manufacturing for clinical studies.
The ability of recombinant adeno-associated viral (rAAV) vectors to exhibit minimal immunogenicity and little to no toxicity or inflammation while eliciting robust, multiyear gene expression in vivo are only a few of the salient features that make them ideally suited for many gene therapy applications. A major hurdle for the use of rAAV in sizeable research and clinical applications is the lack of efficient and versatile large-scale production systems. Continued progression toward flexible, scalable production techniques is a prerequisite to support human clinical evaluation of these novel biotherapeutics. This review examines the current state of large-scale production methods that employ the herpes simplex virus type 1 (HSV) platform to produce rAAV vectors for gene delivery. Improvements have substantially advanced the HSV/AAV hybrid method for large-scale rAAV manufacture, facilitating the generation of highly potent, clinical-grade purity rAAV vector stocks. At least one human clinical trial employing rAAV generated via rHSV helper-assisted replication is poised to commence, highlighting the advances and relevance of this production method.
Clément
Nathalie
N
Department of Pediatrics, Powell Gene Therapy Center, University of Florida, Gainesville, FL 32610, USA.
Knop
David R
DR
Byrne
Barry J
BJ
D002986:Clinical Trials as Topic; D000229:Dependovirus / Q000145:classification / Q000235:genetics* / Q000254:growth & development*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000096:biosynthesis*; D006564:Herpesviridae / Q000235:genetics*; D006801:Humans; D012703:Serotyping