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

Ronald 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

Research output: Contribution to journalArticle

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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 - 1 Jan 1994
Externally publishedYes

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Human Adenoviruses
Cystic Fibrosis
Respiratory System
Complementary DNA
Respiratory Mucosa
Adenoviridae
Nasal Mucosa
Neutralizing Antibodies
Genetic Recombination
Interleukin-6
Epithelium
Phenotype
Lung

ASJC Scopus subject areas

  • Genetics

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Administration of an adenovirus containing the human CFTR cDNA to the respiratory tract of individuals with cystic fibrosis. / Crystal, Ronald; McElvaney, Noel G.; Rosenfeld, Melissa A.; Chu, Chin Shyan; Mastrangeli, Andrea; Hay, John G.; Brody, Steven L.; Jaffe, H. Ari; Eissa, N. Tony; Danel, Claire.

In: Nature Genetics, Vol. 8, No. 1, 01.01.1994, p. 42-51.

Research output: Contribution to journalArticle

Crystal, R, McElvaney, NG, Rosenfeld, MA, Chu, CS, Mastrangeli, A, Hay, JG, Brody, SL, Jaffe, HA, Eissa, NT & Danel, C 1994, 'Administration of an adenovirus containing the human CFTR cDNA to the respiratory tract of individuals with cystic fibrosis', Nature Genetics, vol. 8, no. 1, pp. 42-51. https://doi.org/10.1038/ng0994-42
Crystal, Ronald ; McElvaney, Noel G. ; Rosenfeld, Melissa A. ; Chu, Chin Shyan ; Mastrangeli, Andrea ; Hay, John G. ; Brody, Steven L. ; Jaffe, H. Ari ; Eissa, N. Tony ; Danel, Claire. / Administration of an adenovirus containing the human CFTR cDNA to the respiratory tract of individuals with cystic fibrosis. In: Nature Genetics. 1994 ; Vol. 8, No. 1. pp. 42-51.
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