Repeated adenoviral administration into the biliary tract can induce repeated expression of the original gene construct in rat livers without immunosuppressive strategies

Gut
K TominagaH Fukui

Abstract

Systemic adenoviral readministration appears to be limited by immunogenicity. We examined the feasibility of repeated adenovirus mediated gene transfer into the liver via the biliary tract. Recombinant adenoviruses carrying a reporter lacZ gene were infused retrogradely into the common bile duct of rats. Transduction efficiency of the lacZ gene was estimated histochemically and quantitatively. Retrograde administration of recombinant adenoviruses into the common bile duct of rats resulted in efficient transgene expression in the liver, specifically in hepatocytes, but not in biliary epithelia. Transduction efficiency induced by intrabiliary adenoviral administration was not substantially different from that induced by intraportal adenoviral infusion. Transgene expression in the liver was however transient, and development of neutralising antibodies against adenovirus was observed in serum but not in bile. When adenoviruses were readministered into the common bile duct, successful re-expression of the transgene in the liver was achieved despite the existence of neutralising antibodies in serum. Interestingly, although proliferation of adenovirus specific T cells in response to adenoviral readministration was suppressed significa...Continue Reading

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Citations

Mar 21, 2007·International Journal of Nanomedicine·Hui DaiHai-Quan Mao
Aug 24, 2010·World Journal of Gastroenterology : WJG·Hussein-M Atta
Feb 12, 2009·Hepatology Research : the Official Journal of the Japan Society of Hepatology·Takeshi SudaDexi Liu
Mar 22, 2016·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Julieta MarroneRaúl A Marinelli
Dec 9, 2004·Molecular Therapy : the Journal of the American Society of Gene Therapy·Niek P van TilJurgen Seppen
Apr 9, 2005·Current Opinion in Gastroenterology·Pamela S Tietz, Nicholas F LaRusso
Jun 15, 2006·World Journal of Gastroenterology : WJG·Jesús-M BanalesJuan-F Medina

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