Adeno-associated virus vectorology, manufacturing, and clinical applications

Adeno-associated virus (AAV) has emerged as an attractive vector for gene therapy. The benefits of using AAV for gene therapy include long-term gene expression, the inability to autonomously replicate without a helper virus, transduction of dividing and nondividing cells, and the lack of pathogenicity from wild-type infections. A number of Phase I and Phase II clinical trials utilizing AAV have been carried out worldwide (Aucoin et al., 2008; Mueller and Flotte, 2008). A number of challenges have been identified based upon data generated from these clinical trials. These challenges include (1) large scale manufacturing technologies in accordance with current Good Manufacturing Practices (cGMP), (2) tissue specific tropism of AAV vectors, (3) high-quality/high potency recombinant AAV vectors (rAAV), and (4) immune response to AAV capsids and transgene. In this chapter, we will provide an overview of AAV biology, AAV vectorology, rAAV manufacturing, and the current status on the latest rAAV clinical trials.