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

Y Yang; S E Raper; J A Cohn; J F Engelhardt; J M Wilson

doi:10.1073/pnas.90.10.4601

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

Journal article

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

Y Yang, S E Raper, J A Cohn, J F Engelhardt and J M Wilson

Proceedings of the National Academy of Sciences - PNAS, Vol.90(10), pp.4601-4605

05/15/1993

DOI: 10.1073/pnas.90.10.4601

PMCID: PMC46560

PMID: 7685107

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Abstract

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.

Details

Title: Subtitle: An approach for treating the hepatobiliary disease of cystic fibrosis by somatic gene transfer
Creators: Y Yang - University of Michigan
S E Raper - University of Michigan
J A Cohn - University of Michigan
J F Engelhardt - University of Michigan
J M Wilson - University of Michigan
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.90(10), pp.4601-4605
DOI: 10.1073/pnas.90.10.4601
PMID: 7685107
PMCID: PMC46560
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Language: English
Date published: 05/15/1993
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Radiation Oncology; Internal Medicine
Record Identifier: 9984284452202771

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