Repetitive and safe transgene expression in rat liver is achievable by adenoviral infusion into the common bile duct.
To examine the feasibility of adenovirus-mediated gene transfer into the liver, we examined whether adenoviral infusion into the common bile duct could induce repetitive and safe transgene expression in rat livers. Recombinant adenovirus carrying a reporter lacZ gene was repetitively infused retrogradely into the common bile duct of rats. LacZ expression in rat livers was estimated histochemically by X-gal staining and quantitatively by a chemiluminescent reporter gene assay after the first, second and third adenoviral infusion into the common bile duct. To assess the safety of repetitive adenoviral infusion into the common bile duct, various liver- and kidney-related serum parameters, and liver damage were examined biochemically and histologically, respectively. Retrograde adenoviral infusion into the common bile duct achieved sufficient and safe lacZ expression in rat livers. Although transgene expression in the liver was transient, the second and third adenoviral infusion into the common bile duct could induce the expression of the same transgene in the liver. Furthermore, repetitive adenoviral infusion into the common bile duct caused no significant reverse reactions. Because retrograde adenoviral infusion into the common bile duct is a clinically practical method by using a widely used endoscopic technique, namely endoscopic retrograde cholangiography, these results suggest that retrograde adenoviral infusion into the common bile duct is a practical gene therapy modality in clinical settings.
Kuriyama
Shigeki
S
Third Department of Internal Medicine, Kagawa University School of Medicine, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan. skuriyam@med.kagawa-u.ac.jp
Yoshiji
Hitoshi
H
Tominaga
Kentaro
K
Tsujinoue
Hirohisa
H
Nakatani
Toshiya
T
Tsujimoto
Tatsuhiro
T
Okuda
Hirotsugu
H
Akahane
Takemi
T
Deguchi
Akihiro
A
Nakai
Seiji
S
Masaki
Tsutomu
T
Uchida
Naohito
N
D000256:Adenoviridae / Q000235:genetics*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001806:Blood Urea Nitrogen; D003135:Common Bile Duct; D003404:Creatinine / Q000097:blood; D005260:Female; D015870:Gene Expression; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D007260:Infusion Pumps; D007770:L-Lactate Dehydrogenase / Q000097:blood; D007763:Lac Operon / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D014162:Transfection / Q000379:methods; D019076:Transgenes / Q000235:genetics*; D001616:beta-Galactosidase / Q000378:metabolism
D003404:Creatinine; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001616:beta-Galactosidase