Transduction of renal cells in vitro and in vivo by adeno-associated virus gene therapy vectors.

Published

Journal Article

There has been an increasing interest recently in the possibility of treating renal diseases using gene therapy. The ability to pursue gene therapy for renal diseases has been limited by the availability of an adequate system for gene delivery to the kidney. Adeno-associated virus (AAV) is a defective virus of the parvovirus family that has a number of properties attractive for renal gene delivery: recombinant AAV contains no viral genes; expression of genes delivered by these vectors does not activate cell-mediated immunity; the virus is able to transduce nondividing as well as dividing cells; and both wild-type and recombinant AAV integrate into the host chromosome resulting in long-term gene expression. Studies were performed to determine whether AAV can deliver reporter genes to kidney cells in vitro and in vivo. These studies show that AAV can deliver reporter genes with approximately equal efficiency to human mesangial, proximal tubule, thick ascending limb, collecting tubule, and renal cell carcinoma cells in primary culture. Immortalized mouse mesangial cells are transduced at a much greater efficiency. Transduction can be enhanced by pharmaceutical agents up to sevenfold in primary cells (transducing up to 20% of primary cells per well) and as much as 400-fold in immortalized mesangial cells. AAV delivered in vivo by intraparenchymal injection results in at least 3 mo of reporter gene expression in tubular epithelial, but not glomerular or vascular, cells at the injection site. These data indicate that AAV can deliver genes to renal cells both in vitro and in vivo resulting in prolonged gene expression, and thus AAV can be a useful tool for renal gene delivery.

Full Text

Duke Authors

Cited Authors

  • Lipkowitz, MS; Hanss, B; Tulchin, N; Wilson, PD; Langer, JC; Ross, MD; Kurtzman, GJ; Klotman, PE; Klotman, ME

Published Date

  • September 1999

Published In

Volume / Issue

  • 10 / 9

Start / End Page

  • 1908 - 1915

PubMed ID

  • 10477142

Pubmed Central ID

  • 10477142

International Standard Serial Number (ISSN)

  • 1046-6673

Language

  • eng

Conference Location

  • United States