title: Adeno-associated virus vectors for gene therapy.
abstract: Adeno-associated virus type 2 (AAV) is a non-pathogenic DNA virus which has been utilized as a eukaryotic gene transfer vector in vitro and in vivo. AAV possesses a unique set of characteristics which may make it useful for human gene therapy. AAV infection does not require host cell proliferation, although expression from AAV vectors may exhibit a relative preference for actively dividing cells. Both wild-type AAV and AAV vectors tend to persist in infected cells for prolonged periods of time, without any significant adverse consequences for the host. Wild-type AAV integrates frequently in one specific region of chromosome 19, whereas rep-deleted AAV vectors integrate in a less specific fashion in the host cell genome and may also persist in an episomal state. AAV vectors have been used to transduce a wide range of cell types in vitro including respiratory epithelial cells as well as bone marrow and lymphocyte-derived cells. As a prelude to AAV-based gene therapy for cystic fibrosis (CF), in vivo transduction and expression in the lungs has been observed in rodents and non-human primates after direct delivery to the airway surface, without any detectable toxicity. Based on these findings, the National Institutes of Health Recombinant DNA Advisory Committee (RAC) has recently approved a phase I human trial of CF gene therapy using an AAV vector.
authors.affiliation: Eudowood Division of Pediatric Respiratory Sciences, Johns Hopkins University School of Medicine, Johns Hopkins Hospital, Baltimore, MD 21287-2533, USA.
authors.forename: T R
authors.initials: TR
authors.lastname: Flotte
authors.forename: B J
authors.initials: BJ
authors.lastname: Carter
mesh_terms: D000818:Animals; D002460:Cell Line; D000229:Dependovirus / Q000235:genetics; D005057:Eukaryotic Cells; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D006801:Humans