Gene therapy for the respiratory manifestations of cystic fibrosis

R. J. Korst, N. G. McElvaney, C. S. Chu, M. A. Rosenfeld, A. Mastrangeli, J. Hay, S. L. Brody, N. T. Eissa, C. Danel, H. A. Jaffe, Ronald Crystal

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Cystic fibrosis (CF) is caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The major manifestations are on the airway epithelial surface, with purulent mucus, recurrent infections, chronic inflammation, and loss of lung function. Consequent to mutations in both parental genes, airway epithelial cells have insufficient CFTR function. Because this can be corrected in vitro by transfer of the normal CFTR gene into airway epithelial cells, it is reasonable to hypothesize that the respiratory manifestations of CF could be prevented by transfer of the normal human CFTR cDNA to the airway epithelium in vivo. Over the past 6 years, our laboratory has developed a strategy to accomplish this goal using a replication deficient E1-E3- recombinant adenovirus (Ad) serotype 5 vector containing the normal human CFTR cDNA (AdCFTR). Studies with experimental animals demonstrate that with administration of such a vector to the airways, the human CFTR cDNA could be transferred to the airway epithelium, with expression of the human CFTR cDNA for at least 6 weeks. Extensive preclinical studies in vitro and in vivo demonstrated that the risks to humans were sufficiently low to initiate a Phase I trial using the AdCFTR vector to treat the respiratory manifestations of CF in humans. Following approval by the National Heart, Lung, and Blood Institute Institutional Review Board, the National Institutes of Health Biosafety Committee, the National Institutes of Health Recombinant DNA Advisory Committee, and the Food and Drug Administration, we initiated the first human trial of gene therapy for CF on April 17, 1993. The clinical study is still ongoing, with safety and efficacy data being evaluated, but there is clear evidence that it is feasible to transfer and express the normal CFTR cDNA to the airway epithelium in vivo in individuals with CF.

Original languageEnglish
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume151
Issue number3 II SUPPL.
Publication statusPublished - 1 Jan 1995
Externally publishedYes

Fingerprint

Cystic Fibrosis Transmembrane Conductance Regulator
Cystic Fibrosis
Genetic Therapy
Complementary DNA
Epithelium
National Institutes of Health (U.S.)
Regulator Genes
Epithelial Cells
National Heart, Lung, and Blood Institute (U.S.)
Mutation
Recombinant DNA
Research Ethics Committees
Advisory Committees
United States Food and Drug Administration
Mucus
Adenoviridae
Pneumonia
Safety
Infection

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Cite this

Korst, R. J., McElvaney, N. G., Chu, C. S., Rosenfeld, M. A., Mastrangeli, A., Hay, J., ... Crystal, R. (1995). Gene therapy for the respiratory manifestations of cystic fibrosis. American Journal of Respiratory and Critical Care Medicine, 151(3 II SUPPL.).

Gene therapy for the respiratory manifestations of cystic fibrosis. / Korst, R. J.; McElvaney, N. G.; Chu, C. S.; Rosenfeld, M. A.; Mastrangeli, A.; Hay, J.; Brody, S. L.; Eissa, N. T.; Danel, C.; Jaffe, H. A.; Crystal, Ronald.

In: American Journal of Respiratory and Critical Care Medicine, Vol. 151, No. 3 II SUPPL., 01.01.1995.

Research output: Contribution to journalArticle

Korst, RJ, McElvaney, NG, Chu, CS, Rosenfeld, MA, Mastrangeli, A, Hay, J, Brody, SL, Eissa, NT, Danel, C, Jaffe, HA & Crystal, R 1995, 'Gene therapy for the respiratory manifestations of cystic fibrosis', American Journal of Respiratory and Critical Care Medicine, vol. 151, no. 3 II SUPPL..
Korst RJ, McElvaney NG, Chu CS, Rosenfeld MA, Mastrangeli A, Hay J et al. Gene therapy for the respiratory manifestations of cystic fibrosis. American Journal of Respiratory and Critical Care Medicine. 1995 Jan 1;151(3 II SUPPL.).
Korst, R. J. ; McElvaney, N. G. ; Chu, C. S. ; Rosenfeld, M. A. ; Mastrangeli, A. ; Hay, J. ; Brody, S. L. ; Eissa, N. T. ; Danel, C. ; Jaffe, H. A. ; Crystal, Ronald. / Gene therapy for the respiratory manifestations of cystic fibrosis. In: American Journal of Respiratory and Critical Care Medicine. 1995 ; Vol. 151, No. 3 II SUPPL.
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