AEROSOL-MEDIATED DELIVERY OF RECOMBINANT ADENOVIRUS TO THE AIRWAYS OFNONHUMAN-PRIMATES

At present, it is conceivable that gene therapy of the cystic fibrosis airway epithelium is possible using the direct transfer of a function al human cystic fibrosis transmembrane conductance regulator (CFTR) ge ne to a wide variety of patients' tracheo-bronchial cells. Here we des cribe a novel approach (aerosolization) to deliver a replication-defic ient adenovirus carrying the CFTR gene (Ad.CFTR) to the airways. Resul ts obtained in vitro and in Rhesus monkeys suggest that the delivery o f recombinant adenovirus as an aerosol is feasible and is not associat ed with severe toxicity after single or double administration dependin g on the Ad.CFTR dose. This study supports the concept of aerosolizati on as a delivery method for adenovirus-mediated lung gene therapy.