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Liposome-mediated CFTR gene transfer to the nasal epithelium of patients with cystic fibrosis

An Erratum to this article was published on 01 March 1995

This article has been updated

Abstract

We report the results of a double-blind, placebo-controlled trial in nine cystic fibrosis (CF) subjects receiving cationic liposome complexed with a complementary DNA encoding the CF transmembrane conductance regulator (CFTR), and six CF subjects receiving only liposome to the nasal epithelium. No adverse clinical effects were seen and nasal biopsies showed no histological or immuno-histological changes. A partial restoration of the deficit between CF and non-CF subjects of 20% was seen for the response to low Cl− perfusion following CFTR cDNA administration. This was maximal around day three and had reverted to pretreatment values by day seven. In some cases the response to low Cl− was within the range for non-CF subjects. Plasmid DNA and transgene-derived RNA were detected in the majority of treated subjects. Although these data are encouraging, it is likely that transfection efficiency and the duration of expression will need to be increased for therapeutic benefit.

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  • 01 March 1995

    In the January issue of Nature Medicine, an error in typography resulted in the incorrect printing of the Greek characters and μ. This error affected several papers. Nature Medicine regrets the errors, and all reprints of the articles have been corrected. Liposome-mediated CFTR gene transfer to the nasal epithelium of patients with cystic fibrosis Natasha J.

References

  1. Riordan, J.R. et al. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 245, 1066–1073 (1989).

    Article  CAS  Google Scholar 

  2. Welsh, M.J. Abnormal regulation of ion channel) in cystic fibrosis epithelia. FASEB J. 4, 2718–2725 (1990).

    Article  CAS  Google Scholar 

  3. Knowles, M.R., Gatzy, J.T. & Boucher, R.C. Increased bioelectric potential difference across respiratory epithelia in cystic fibrosis. N. Engl. J. Med. 305, 1489–1495 (1981).

    Article  CAS  Google Scholar 

  4. Hardcastle, J., Hardcastle, P.T., Taylor, C.J. & Goldhill, J. Failure of cholinergic stimulation to induce a secretory response from the rectal mucosa in cystic fibrosis. Gut 32, 1035–1039 (1991).

    Article  CAS  Google Scholar 

  5. 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 

  6. Rich, D.P. et al. Expression of 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 

  7. Alton, E.W.F.W. et al. Non-invasive liposome-mediated gene delivery can correct the ion transport defect in cystic fibrosis mutant mice. Nature Genet. 5, 135–142 (1993).

    Article  CAS  Google Scholar 

  8. Hyde, S. et al. Correction of the ion transport defect in cystic fibrosis transgenic mice by gene therapy. Nature 362, 250–255 (1993).

    Article  CAS  Google Scholar 

  9. Collins, F.S., Molecular biology and therapeutic implications. Science 256, 774–779 (1992).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  11. Crystal, R.C. et al. Protocol for gene therapy of the respiratory manifestations of cystic fibrosis using a replication deficient, recombinant adenovirus to transfer the normal human cystic fibrosis transmembrane conductance regulator cDNA to the airway epithelium. Federal Register 57, 49584. (1992).

    Google Scholar 

  12. Welsh, M.J. et al. Clinical Protocol. Cystic fibrosis gene therapy using adenovirus vector: In vivo safety and efficacy in nasal epithelium. Hum. gene Ther. 5, 209–219 (1994).

    Article  CAS  Google Scholar 

  13. Wilson, J.M., Engelhardt, J.F., Grossman, M., Simon, R.H. & Yang, Y., Clinical Protocol: Gene therapy of cystic fibrosis lung disease using El deleted adenovirus: a phase 1 trial. Hum. gene Ther. (In the Press 1994).

  14. Boucher, R.C. et al. Gene therapy for cystic fibrosis using E1-deleted adenovirus: a Phase I trial in the nasal cavity. Hum. gene Ther. 5, 501–519 (1994).

    Article  Google Scholar 

  15. Zabner, J. et al. Adenovirus-mediated gene transfer transiently corrects the chloride transport defect in nasal epithelia of patients with cystic fibrosis. Cell 75, 1–20 (1993).

    Article  Google Scholar 

  16. Crystal, R.G. et al. Administration of an adenovirus containing the human CFTR cDNA to the respiratory tract of individuals with cystic fibrosis. Nature Genet. 8, 42–51 (1994).

    Article  CAS  Google Scholar 

  17. Smith, T.A.G. et al. Adenovirus mediated express levels of human factor IX in mice. Nature Genet. 5, 397–402 (1993).

    Article  CAS  Google Scholar 

  18. Yei, S., Mittereder, N., Tang, K., O'Sullivan, C. & Trapnell, B.C. Adenovirus-mediated gene transfer for cystic fibrosis. Quantitative evaluation of repeated in vivo vector administration to the lung. Gene Ther. 1, 192–200 (1994).

    CAS  PubMed  Google Scholar 

  19. Gao, X. & Haung, L. A novel cationic liposome reagent for efficient transfection of mammalian cells. Biochem. Biophys. Res. Comm. 179, 280–285 (1991).

    Article  CAS  Google Scholar 

  20. Varney, V.A. et al. Immunohistology of the nasal mucosa following allergen-induced rhinitis. Identification of activated T-lymphocytes, eosinophils and neutrophils. Am. Rev. respir. Dis. 145, 170–176 (1992).

    Article  Google Scholar 

  21. Alton, E.W.F.W. et al. Nasal potential difference: A clinical diagnostic test for cystic fibrosis. Eur. Resp. J. 3, 922–926 (1990).

    CAS  Google Scholar 

  22. Middleton, P.G. et al. Nasal application of the cationic liposome DC-Chol:DOPE does not alter ion transport, lung function or bacterial growth. Eur. Resp. J. 7, 442–445 (1994).

    Article  CAS  Google Scholar 

  23. Middleton, P.G., Geddes, D.M. & Alton, E.W.F.W. Protocols for in vivo meaurement for ion transport defects in cystic fibrosis nasal epithelium. Eur. Resp. J.

  24. Nabel, E.G. et al. Gene transfer in vivo with DNA-Liposome complexes: Lack of autoimmunity and gonadal localization. Hum. gene Ther. 3, 649–656 (1992).

    Article  CAS  Google Scholar 

  25. Wilson, R. et al. Upper respiratory tract viral infection and mucociliary clearance Eur. J. Resp. Dis., 70,, 272–279 (1987).

    CAS  Google Scholar 

  26. Fokkens, W.J., Vroom, T.M., Gerritsma, V. & Rijntes, E. A biopsy method to obtain high quality specimens of nasal mucosa. Rhinology 26, 293–295 (1988).

    CAS  PubMed  Google Scholar 

  27. Mason, D.Y. et al. Detection of T cells in paraffin wax embedded tissue using antibodies against a peptide sequence from CD3 antigen. J. Clin. Pathol. 42, 1194–1120 (1989).

    Article  CAS  Google Scholar 

  28. Caplen, N.J. et al. Gene therapy for cystic fibrosis in humans by liposome-mediated DNA transfer the production of resources and the regulatory process. Gene Ther. 1, 139–147 (1994).

    CAS  PubMed  Google Scholar 

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Caplen, N., Alton, E., Mddleton, P. et al. Liposome-mediated CFTR gene transfer to the nasal epithelium of patients with cystic fibrosis. Nat Med 1, 39–46 (1995). https://doi.org/10.1038/nm0195-39

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