Administration of an adenovirus containing the human CFTR cDNA to the respiratory tract of individuals with cystic fibrosis

Ronald G. Crystal, Noel G. McElvaney, Melissa A. Rosenfeld, Chin Shyan Chu, Andrea Mastrangeli, John G. Hay, Steven L. Brody, H. Ari Jaffe, N. Tony Eissa, Claire Danel

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Abstract

We have administered a recombinant adenovirus vector (AdCFTR) containing the normal human CFTR cDNA to the nasal and bronchial epithelium of four individuals with cystic fibrosis (CF). We show that this vector can express the CFTR cDNA in the CF respiratory epithelium in vivo. With doses up to 2 × 109 pfu, there was no recombination/complementation or shedding of the vector or rise of neutralizing antibody titres. At 2 × 109 pfu, a transient systemic and pulmonary syndrome was observed, possibly mediated by interleukin-6. Follow-up at 6–12 months demonstrated no long term adverse effects. Thus, it is feasible to use an adenovirus vector to transfer and express the CFTR cDNA in the respiratory epithelium of individuals with CF. Correction of the CF phenotype of the airway epithelium might be achieved with this strategy.

Original languageEnglish
Pages (from-to)42-51
Number of pages10
JournalNature Genetics
Volume8
Issue number1
DOIs
Publication statusPublished - Sep 1994

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ASJC Scopus subject areas

  • Genetics

Cite this

Crystal, R. G., McElvaney, N. G., Rosenfeld, M. A., Chu, C. S., Mastrangeli, A., Hay, J. G., Brody, S. L., Jaffe, H. A., Eissa, N. T., & Danel, C. (1994). Administration of an adenovirus containing the human CFTR cDNA to the respiratory tract of individuals with cystic fibrosis. Nature Genetics, 8(1), 42-51. https://doi.org/10.1038/ng0994-42