An approach for treating the hepatobiliary disease of cystic fibrosis by somatic gene transfer.

Published

Journal Article

Cystic fibrosis (CF) is an inherited disease of epithelial cell ion transport that is associated with pathology in multiple organ systems, including lung, pancreas, and liver. As treatment of the pulmonary manifestations of CF has improved, management of CF liver disease has become increasingly important in adult patients. This report describes an approach for treating CF liver disease by somatic gene transfer. In situ hybridization and immunocytochemistry analysis of rat liver sections indicated that the endogenous CFTR (cystic fibrosis transmembrane conductance regulator) gene is primarily expressed in the intrahepatic biliary epithelial cells. To specifically target recombinant genes to the biliary epithelium in vivo, recombinant adenoviruses expressing lacZ or human CFTR were infused retrograde into the biliary tract through the common bile duct. Conditions were established for achieving recombinant gene expression in virtually all cells of the intrahepatic bile ducts in vivo. Expression persisted in the smaller bile ducts for the duration of the experiment, which was 21 days. These studies suggest that it may be feasible to prevent CF liver disease by genetically reconstituting CFTR expression in the biliary tract, using an approach that is clinically feasible.

Full Text

Duke Authors

Cited Authors

  • Yang, Y; Raper, SE; Cohn, JA; Engelhardt, JF; Wilson, JM

Published Date

  • May 15, 1993

Published In

Volume / Issue

  • 90 / 10

Start / End Page

  • 4601 - 4605

PubMed ID

  • 7685107

Pubmed Central ID

  • 7685107

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.90.10.4601

Language

  • eng

Conference Location

  • United States