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

Nature Genetics volume 9, pages 126–131 (1995)Cite this article

Abstract

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.

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Authors and Affiliations

  1. Institute for Human Gene Therapy,

    Mitchell J. Goldman, Yiping Yang & James M. Wilson

  2. Departments of Medicine,

    Mitchell J. Goldman, Yiping Yang & James M. Wilson

  3. Molecular and Cellular Engineering, University of Pennsylvania Medical Center and The Wistar Institute, Philadelphia, Pennsylvania, 19104, USA

    Mitchell J. Goldman, Yiping Yang & James M. Wilson

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  1. Mitchell J. Goldman
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  2. Yiping Yang
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  3. James M. Wilson
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Goldman, M., Yang, Y. & Wilson, J. Gene therapy in a xenograft model of cystic fibrosis lung corrects chloride transport more effectively than the sodium defect. Nat Genet 9, 126–131 (1995). https://doi.org/10.1038/ng0295-126

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