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Adeno-associated virus vectors for gene therapy.

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.[1]

References

  1. Adeno-associated virus vectors for gene therapy. Flotte, T.R., Carter, B.J. Gene Ther. (1995) [Pubmed]
 
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