Administration of an adenovirus containing the human CFTR cDNA to the respiratory tract of individuals with cystic fibrosis
| Autor: | Andrea Mastrangeli, Steven L. Brody, Chin-Shyan Chu, H A Jaffe, Claire Danel, Melissa A. Rosenfeld, J. G. Hay, N. T. Eissa, Ronald G. Crystal, Noel G. McElvaney |
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| Rok vydání: | 1994 |
| Předmět: |
Adult
Male DNA Complementary Cystic Fibrosis Genetic enhancement Genetic Vectors Molecular Sequence Data Respiratory System DNA Recombinant Cystic Fibrosis Transmembrane Conductance Regulator Bronchi Nose medicine.disease_cause Cystic fibrosis Epithelium Adenoviridae Genetics medicine Humans Lung biology Base Sequence Interleukin-6 Membrane Proteins Genetic Therapy respiratory system biology.organism_classification medicine.disease Virology Cystic fibrosis transmembrane conductance regulator Mastadenovirus Radiography medicine.anatomical_structure biology.protein Respiratory epithelium Female Respiratory tract |
| Zdroj: | Nature genetics. 8(1) |
| ISSN: | 1061-4036 |
| Popis: | 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 x 10(9) pfu, there was no recombination/complementation or shedding of the vector or rise of neutralizing antibody titres. At 2 x 10(9) 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. |
| Databáze: | OpenAIRE |
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