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lüll Recombinant adeno-associated virus transduction and integration Schultz BR; Chamberlain JSMol Ther 2008[Jul]; 16 (7): 1189-99Recombinant adeno-associated virus (rAAV) holds promise as a gene therapy vector for a multitude of genetic disorders such as hemophilia, cystic fibrosis, and the muscular dystrophies. Given the variety of applications and tissue types toward which these vectors may be targeted, an understanding of rAAV transduction is crucial for the effective application of therapy. rAAV transduction mechanisms have been the subject of much study, resulting in a body of knowledge relating to events from virus-cell attachment through to vector genome conformation in the target cell nucleus. Instead of utilizing one mechanism in each phase of vector transduction, rAAV appears to employ multiple possible pathways toward transgene expression, in part dependent on rAAV serotype, dose, and target cell type. Once inside the nucleus, the rAAV genome exists in a predominantly episomal form; therefore, nondividing cells tend to be most stably transduced. However, rAAV has a low frequency of integration into the host cell genome, often in or near genes, and can be associated with host genome mutations. This review describes the current understanding of the mechanisms and rate-limiting steps involved in rAAV transduction.|*Genetic Therapy[MESH]|*Transduction, Genetic[MESH]|*Virus Integration[MESH]|Animals[MESH]|DNA, Recombinant/genetics[MESH]|Dependovirus/genetics/*physiology[MESH]|Genetic Vectors/genetics/*physiology[MESH]|Humans[MESH]|Mice[MESH]|Virus Internalization[MESH] |