Gene therapy in a xenograft model of cystic fibrosis lung corrects chloride transport more effectively than the sodium defect.


Journal Article

We have developed a model of gene therapy for cystic fibrosis (CF) lung disease, based on growth of human CF bronchial xenografts in nu/nu mice. We now report an evaluation of the primary abnormalities in CF lung epithelia--defective Cl secretion and Na hyperabsorption--in xenografts following adenovirus-mediated gene transfer. In vivo infection of CF xenografts with a cystic fibrosis transmembrane regulator (CFTR) recombinant adenovirus, at a multiplicity of infection equal to 100, was sufficient to reconstitute near normal levels of cAMP-stimulated Cl transport, despite transducing only 5% of cells in the pseudostratified epithelium. Correction in sodium hyperabsorption was partial and variable. These experiments define aspects of adenovirus-mediated gene therapy relevant to CF protocols based on intrapulmonary genetic reconstitution.

Full Text

Cited Authors

  • Goldman, MJ; Yang, Y; Wilson, JM

Published Date

  • February 1995

Published In

Volume / Issue

  • 9 / 2

Start / End Page

  • 126 - 131

PubMed ID

  • 7719338

Pubmed Central ID

  • 7719338

Electronic International Standard Serial Number (EISSN)

  • 1546-1718

International Standard Serial Number (ISSN)

  • 1061-4036

Digital Object Identifier (DOI)

  • 10.1038/ng0295-126


  • eng