ADMINISTRATION OF AN ADENOVIRUS CONTAINING THE HUMAN CFTR CDNA TO THERESPIRATORY-TRACT OF INDIVIDUALS WITH CYSTIC-FIBROSIS

We have administered a recombinant adenovirus vector (AdCFTR) containi ng 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. Wi th doses up to 2 x 10(9) pfu, there was no recombination/ complementat ion or shedding of the vector or rise of neutralizing antibody titres. At 2 x 10(9) pfu, a transient systemic and pulmonary syndrome was obs erved, possibly mediated by interleukin-6. Follow-up at 6-12 months de monstrated no long term adverse effects. Thus, it is feasible to use a n adenovirus vector to transfer and express the CFTR cDNA in the respi ratory epithelium of individuals with CF. Correction of the CF phenoty pe of the airway epithelium might be achieved with this strategy.