ADENOASSOCIATED VIRUS VECTORS FOR GENE-THERAPY OF NEURODEGENERATIVE DISORDERS

Adeno-associated virus (AAV) shows significant potential as a gene del ivery system. Although it is ubiquitous in its distribution, with appr oximately 85% of the adult population in the United States seropositiv e for the virus [1], it has never been associated with clinical diseas e. Not only is AAV non-pathogenic, but it can infect with high efficie ncy both dividing and terminally-differentiated cells, moreover the wi ld-type virus integrates into a specific chromosomal site [2-5]. It al so has a broad host range and the virus is extremely resistant to envi ronmental extremes. These characteristics make it particularly attract ive as a gene delivery vehicle. As the enthusiasm driving the prolifer ation of clinical gene transfer protocols has dampened recently due to the lack of clinical success often reflecting immunogenicity and inef ficiency of the gene transfer methods used in these trials, AAV with m inimal (if any) toxicity and high efficiency in a wide range of cells and tissues, may become the vector-of-choice for many applications. Th ere have been a number of comprehensive recent reviews of AAV biology [6-11] 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. (C) 1996 W iley-Liss, Inc.