Successful Gene Transfer Using Adeno-Associated Virus Vectors into the Kidney: Comparison among Adeno-Associated Virus Serotype 1–5 Vectors in vitro and in vivo

Abstract

Background/Aim: Gene transfer into the kidney has great potential as a novel therapeutic approach. However, an efficient method of gene transfer into the kidney has not been established. We explored the transduction efficiency of renal cells in vitro and in vivo using adeno-associated virus (AAV) serotype 1–5 vectors encoding the β-galactosidase gene. Methods: In the in vitro study, rat kidney epithelial cell line NRK52E cells were transfected with AAV serotype derived vectors. In the in vivo study, AAV serotype derived vectors were selectively injected into the kidney using a catheter-based gene delivery system in rats and mice mimicking the clinical procedure. The efficiency of gene expression was histologically evaluated on the basis of the β-galactosidase expression. Results: AAV serotype 1, 2, and 5 vectors transduced in rat kidney epithelial cell line NRK52E cells in vitro, whereas AAV serotype 3 or 4 vectors showed no transduction. In addition, the kidney-specific injection of AAV serotype 2 vectors successfully transduced in tubular epithelial cells, but not in glomerular, blood vessel, or interstitial cells in vivo, whereas the rest of the serotypes showed no transduction. Conclusion: Since kidney-specific gene delivery via the renal artery by catheterization is highly feasible in humans, these findings provide useful information for promising strategies in renal gene therapy.

Adeno-Associated Virus Vectors: Versatile Tools for in vivo Gene Transfer

“…Finally, among the new rAAV serotype variants, the efficiency of AAV1-5 has been investigated in renal cells in vitro and in vivo [39]. AAV vectors of serotypes 1, 2, and 5 were shown to transduce renal epithelial cell lines with good efficiency in vitro, whereas AAV serotype 2 proved to be the most efficient for the transduction of the tubular epithelial cells in vivo [39].…”

PEG conjugation moderately protects adeno-associated viral vectors against antibody neutralization

“…Recombinant AAV (rAAV) vectors are non-pathogenic, have the ability to transduce a wide range of tissues (Flannery et al, 1997;Herzog, 2004;Herzog and High, 1999;Kaspar et al, 2002b;Miao et al, 2000;Takeda et al, 2004;Tenenbaum et al, 2004), and are capable of stable integration or episomal maintenance resulting in long-term transgene expression Duan et al, 1998;Flotte et al, 1994;Kearns et al, 1996;Nakai et al, 1999). Over 90% of the human population is seropositive for anti-AAV2 antibodies, with no associated disease.…”

Characterization of the Adeno-Associated Virus 1 and 6 Sialic Acid Binding Site

“…Due to their nonpathogenicity, ability to package recombinant DNA, long-term transgene expression, and ability to transduce dividing and nondividing cells, the AAVs are being developed as gene delivery vectors (7,8). The most studied serotype, AAV2, exhibits broad tissue tropism, while several other serotypes exhibit better specific tissue transduction (9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Examples include AAV1 transduction of smooth muscle, the central nervous system, and retina at 1,000-, 35-, and 2-fold better, respectively (13)(14)(15), while AAV6 has superior smooth muscle, heart, and lung transduction by 500-, 10-, and 10-fold, respectively, compared to AAV2 (16)(17)(18).…”