A denoassociated virus (AAV) has emerged as the leading vector for gene therapy delivery. Compared with options such as lentivirus and adenovirus, AAV exhibits a strong safety profile because it has low pathogenicity and requires a helper virus to replicate. AAV is also capable of long-term gene expression, and it can infect both dividing and nondividing cells (1-5). Developers of advanced therapies have found such advantages to be quite attractive. As of January 2021, two gene therapy products havegained US Food and Drug Administration (FDA) approval: Luxturna (voretigene neparvovec) from Spark Therapeutics and Zolgensma (onasemnogene abeparvovec) from AveXis/Novartis. Both products use AAV vectors (serotypes 2 and 9, respectively), as do many candidate therapies moving through clinical studies. Cost-effective AAV manufacturing remains elusive, however. Yields and expression titers from upstream processes continue to be low — an acute problem for a modality that requires doses with high vector concentrations.
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