Production of recombinant adeno-associated virus.

Currently, rAAV appears to be one of the most promising vectors for gene therapy applications. Attractive features of the vector include nonpathogenicity, the ability to infect nondividing cells, escape from host immune responses, and integration into the host genome. Tremendous progress has been made in the production of this vector, which makes it possible to start to examine the vector performance in large animals and to implement the transition to phase I human clinical trials with a variety of target tissues and therapeutic genes. However, some major challenges remain to be addressed by more extensive studies. These include the current inability to provide rAAV vectors in sufficient quantity and purity for large-scale clinical human applications, lack of site-specific integration, and lack of efficient transduction in some tissues such as airway epithelial cells. There is a limited transgene capacity in recombinant virus particles, and repeated administration of the vectors may be necessary to treat patients with chronic forms of genetic disease. Nevertheless, it is reasonable to assume that significant refinements will be made in all these areas in the relatively near future. This will promote the potential for successful therapeutic applications in humans, using rAAV-mediated gene transfer for a variety of different diseases.