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.
OBJECTIVE
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 beta-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 beta-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.


CONCLUSIONS
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.
Takeda
Shin-ichi
S
Division of Organ Replacement Research, Center for Molecular Medicine, Jichi Medical School, Tochigi, Japan. masafumi@jichi.ac.jp
Takahashi
Masafumi
M
Mizukami
Hiroaki
H
Kobayashi
Eiji
E
Takeuchi
Koichi
K
Hakamata
Yoji
Y
Kaneko
Takashi
T
Yamamoto
Hisashi
H
Ito
Chiharu
C
Ozawa
Keiya
K
Ishibashi
Kenichi
K
Matsuzaki
Toshiyuki
T
Takata
Kuniaki
K
Asano
Yasushi
Y
Kusano
Eiji
E
D000818:Animals; D002404:Catheterization; D002460:Cell Line; D000229:Dependovirus / Q000145:classification / Q000235:genetics*; D005822:Genetic Vectors / Q000008:administration & dosage; D007668:Kidney / Q000033:anatomy & histology / Q000378:metabolism*; D008297:Male; D051379:Mice; D051381:Rats; D011917:Rats, Inbred Lew; D014161:Transduction, Genetic / Q000379:methods*