Correction of the apical membrane chloride permeability defect in polarized cystic fibrosis airway epithelia following retroviral-mediated gene transfer

John C. Olsen, Larry G. Johnson, M. Jackson Stutts, Balazs Sarkadi, James R. Yankaskas, Ronald Swanstrom, Richard C. Boucher

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

We are studying the introduction and expression of the normal cystic fibrosis transmembrane conductance regulator (CFTR) cDNA into cultured human airway epithelial cells as a model for gene therapy of cystic fibrosis. In this paper, we show that the chloride transport defect at the apical membrane is corrected in vitro in differentiated ion-transporting CF airway epithelial cells that exhibit polarized properties similar to those found in vivo. Using a retroviral vector containing a copy of the normal CFTR cDNA, we infected cultures of proliferating, cystic fibrosis CFT1 cells and found that correction was maintained following differentiation into a polarized epithelial sheet. At least partial correction of the Cl- transport defect was preserved in CFT1 cells for periods of up to 6 months without selection for maintenance of the retroviral provirus. These results suggest that it may be feasible to target proliferating cells in the lung using retroviral vectors for treatment of CF lung disease.

Original languageEnglish
Pages (from-to)253-266
Number of pages14
JournalHuman Gene Therapy
Volume3
Issue number3
DOIs
Publication statusPublished - 1992

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

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