Adeno-associated virus vectors for gene therapy of neurodegenerative disorders

Adeno-associated virus (AAV) shows significant potential as a gene delivery system. Although it is ubiquitous in its distribution, with approximately 85% of the adult population in the United States seropositive for the virus, it has never been associated with clinical disease. Not only is AAV non-pathogenic, but it can infect with high efficiency both dividing and terminally-differentiated cells, moreover the wild-type virus integrates into a specific chromosomal site. It also has a broad host range and the virus is extremely resistant to environmental extremes. These characteristics make it particularly attractive as a gene delivery vehicle. As the enthusiasm driving the proliferation of clinical gene transfer protocols has dampened recently due to the lack of clinical success often reflecting immunogenicity and inefficiency of the gene transfer methods used in these trials, AAV with minimal (if any) toxicity and high efficiency in a wide range of cells and tissues, may become the vector-of-choice for many applications. There have been a number of comprehensive recent reviews of AAV biology and this article specifically discusses recent advances in the use of AAV vectors with particular emphasis on AAV vector-mediated in vivo gene transfer in the mammalian central nervous system.