Adeno-associated virus vectors for gene therapy

Gene Ther. 1995 Aug;2(6):357-62.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Cell Line
  • Dependovirus* / genetics
  • Eukaryotic Cells
  • Gene Transfer Techniques
  • Genetic Therapy / methods*
  • Genetic Vectors*
  • Humans