Integration of adeno-associated virus (AAV) and recombinant AAV vectors.
The driving interest in adeno-associated virus (AAV) has been its potential as a gene delivery vector. The early observation that AAV can establish a latent infection by integrating into the host chromosome has been central to this interest. However, chromosomal integration is a two-edged sword, imparting on one hand the ability to maintain the therapeutic gene in progeny cells, and on the other hand, the risk of mutations that are deleterious to the host. A clearer understanding of the mechanism and efficiency of AAV integration, in terms of contributing viral and host-cell factors and circumstances, will provide a context in which to evaluate these potential benefits and risks. Research to date suggests that AAV integration in any context is inefficient, and that the persistence of AAV gene delivery vectors in tissues is largely attributable to episomal genomes.
McCarty
Douglas M
DM
School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599, USA. mccarty@med.unc.edu
Young
Samuel M
SM
Samulski
R Jude
RJ
D002460:Cell Line; D002888:Chromosomes, Human, Pair 19 / Q000821:virology; D004247:DNA / Q000235:genetics; D000229:Dependovirus / Q000235:genetics* / Q000502:physiology; D015316:Genetic Therapy; D005822:Genetic Vectors; D016679:Genome, Viral; D006367:HeLa Cells; D006801:Humans; D011995:Recombination, Genetic; D016662:Virus Integration
D004247:DNA