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Efficiency of gene transfer for restoration of normal airway epithelial function in cystic fibrosis

Nature Genetics volume 2, pages 21–25 (1992)Cite this article

Abstract

An important issue for in vivo gene therapy for cystic fibrosis (CF) is the percentage of cells within the CF airway that will require correction. In this study, we mixed populations of a CF airway cell line expressing either the normal cystic fibrosis transmembrane conductance regulator (CFTR) cDNA (corrected cells) or a reporter gene in defined percentages. As few as 6–10% corrected cells within an epithelial sheet generated Cl− transport properties similar to sheets comprised of 100% corrected cells. Cell–cell coupling may serve as the mechanism for amplification of the functional effects of corrected cells. These data suggest that in vivo correction of all CF airway cells may not be mandatory.

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References

  1. Boat, T.F., Welsh, M.J. & Beaudet, A.L. Cystic fibrosis. in The Metabolic Basis of Inherited Disease, (eds. Scriver C.R., Beaudet, A.L., Sly, W.S. & D. valle) 2649–2680 (McGraw Hill, New York, 1989).

    Google Scholar 

  2. Quinton, P. Cystic fibrosis: a disease in electrolyte transport. FASEB J. 4, 2709–2717 (1990).

    Article  CAS  Google Scholar 

  3. Quinton, P.M. Chloride impermeability in cystic fibrosis. Nature 301, 421–422 (1983).

    Article  CAS  Google Scholar 

  4. Quinton, P.M. & Bijman, J. Higher bioelectric potentials due to decreased chloride absorption in the sweat glands of patients with cystic fibrosis. New Engl. J. Med. 308, 1185–1188 (1983).

    Article  CAS  Google Scholar 

  5. Knowles, M.R. et al. Abnormal ion permeation through cystic fibrosis respiratory epithelium. Science 221, 1067–1070 (1983).

    Article  CAS  Google Scholar 

  6. Knowles, M., Gatzy, J. & Boucher, R. Relative ion permeability of normal & cystic fibrosis nasal epithelium. J. clin. Invest. 71, 1410–1417 (1983).

    Article  CAS  Google Scholar 

  7. Drumm, M.L. et al. Correction of the cystic fibrosis defect in vitro by retrovirus-mediated gene transfer. Cell 62, 1227–1233 (1990).

    Article  CAS  Google Scholar 

  8. Rich, D.P. et al. Expression of the cystic fibrosis transmembrane conductance regulator corrects defective chloride channel regulation in cystic fibrosis airway epithelial cells. Nature 347, 358–363 (1990).

    Article  CAS  Google Scholar 

  9. Olsen, J.C. et al. Correction of the apical membrane chloride permeability defect in polarized cystic fibrosis airway epithelia following retroviral-mediated gene transfer. Hum. Gene Therapy 3, 253–266 (1992).

    Article  CAS  Google Scholar 

  10. Rosenfeld, M.A. et al. In vivo transfer of the human cystic fibrosis transmembrane conductance regulator to the airway epithelium. Cell 68, 143–155 (1992).

    Article  CAS  Google Scholar 

  11. Willumsen, N.J., Davis, C.W. & Boucher, R.C. Intracellular Cl− activity & cellular pathways in cultured human airway epithelium. Am. J. Physiol. 256, C1033–1044 (1989).

    Article  CAS  Google Scholar 

  12. Willumsen, N.J. & Boucher, R.C. Shunt resistance & ion permeabilities in normal & cystic fibrosis airway epithelium. Am. J. Physiol. 256, C1054–1063 (1989).

    Article  CAS  Google Scholar 

  13. Willumsen, N.J., Davis, C.W. & Boucher, R.C. Cellular Cl− transport in cultured cystic fibrosis airway epithelium. Am. J. Physiol. 256, C1045–C1053 (1989).

    Article  CAS  Google Scholar 

  14. Boucher, R.C., Stutts, M.J., Knowles, M.R., Cantley, L. & Gatzy, J.T. Na+ transport in cystic fibrosis respiratory epithelia: abnormal basal rate & response to adenylate cyclase activation. J. clin. Invest. 78, 1245–1252 (1986).

    Article  CAS  Google Scholar 

  15. Yankaskas, J.R., Knowles, M.R., Gatzy, J.T. & Boucher, R.C. Persistence of abnormal chloride ion permeability in cystic fibrosis nasal epithelial cells in heterologous culture. Lancet 1, 954–956 (1985).

    Article  CAS  Google Scholar 

  16. Flagg-Newton, J., Simpson, I. & Loewenstein, W.R. Permeability of the cell-to-cell membrane channels in mammalian cell junction. Science 205, 404–407 (1979).

    Article  CAS  Google Scholar 

  17. Sarkadi, B. et al. Biochemical characterization of the cystic fibrosis transmembrane conductance regulator in normal & cystic fibrosis epithelial cells. J. biol. Chem. 267, 2087–2095 (1992).

    CAS  Google Scholar 

  18. Cotton, C.U., Stutts, M.J., Knowles, M.R., Gatzy, J.T. & Boucher, R.C. Abnormal apical cell membrane in cystic fibrosis respiratory epithelium: an in vitro electrophysiologic analysis. J. clin. Invest. 79, 80–85 (1987).

    Article  CAS  Google Scholar 

  19. Cheng, S.H. et al. Defective intracellular transport and processing of CFTR is the molecular basis of most cystic fibrosis. Cell 63, 827–834 (1990).

    Article  CAS  Google Scholar 

  20. Sanderson, M.J., Chow, I. & Dirksen, E.R. Intercellular communication between ciliated cells in culture. Am. J. Physiol. 254, C63–C74 (1988).

    Article  CAS  Google Scholar 

  21. Inoue, S. & Hogg, J.C. Intercellular junctions of the tracheal epithelium in guinea pigs. Lab. Invest. 31, 68–74 (1974).

    CAS  PubMed  Google Scholar 

  22. Carson, J.L., Willumsen, N.J., Gambling, T.M., Hu, S.-C.S. & Collier, A.M. Dynamics of intracellular communications & differentiation in a rapidly developing mammalian airway epithelium. Am. J. Resp. Cell molec. Biol. 1, 385–390 (1989).

    Article  CAS  Google Scholar 

  23. Schneeberger, E.E., Walters, D.V. & Olver, R.E. Development of intercellular junctions in the pulmonary epithelium of the foetal lamb. J. Cell Science 32, 307–324 (1978).

    CAS  PubMed  Google Scholar 

  24. Miller, A.D. & Rosman, G.J. Improved retroviral vectors for gene transfer and expression. Biotechniques 7, 980–990 (1990).

    Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599-7020, USA

    Larry G. Johnson, Karen L. Moore & Richard C. Boucher

  2. Department of Biochemistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599-7020, USA

    Ronald Swanstrom

  3. Department of The Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, 27599-7020, USA

    John C. Olsen & Ronald Swanstrom

  4. National Institute of Haematology and Blood Transfusion, Budapest, Hungary

    Balazs Sarkadi

Authors
  1. Larry G. Johnson
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  2. John C. Olsen
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  3. Balazs Sarkadi
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  4. Karen L. Moore
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  5. Ronald Swanstrom
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  6. Richard C. Boucher
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Johnson, L., Olsen, J., Sarkadi, B. et al. Efficiency of gene transfer for restoration of normal airway epithelial function in cystic fibrosis. Nat Genet 2, 21–25 (1992). https://doi.org/10.1038/ng0992-21

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