A chimeric type 2 adenovirus vector with a type 17 fiber enhances gene transfer to human airway epithelia

In studies of the genetic disease cystic fibrosis, recombinant adenovirus t ype 2 (Ad2) and Ad5 are being investigated as vectors to transfer cystic fi brosis transmembrane conductance regulator cDNA to airway epithelia. Howeve r, earlier work has shown that human airway epithelia are resistant to infe ction by Ad2 and Ad5. Therefore, we examined the efficiency of other adenov irus serotypes at infecting airway epithelia. We found that several serotyp es of adenoviruses, in particular, wild-type Ad17, infected a greater numbe r of cells than wild-type Ad2. The increased efficiency of wild-type Ad17 c ould be explained by increased fiber-dependent binding to the epithelia. Th erefore, we constructed a chimeric virus, Ad2(17f)beta Gal-2, which is iden tical to Ad2/beta Gal-2 with the exception of having the fiber protein of A d17 replace Ad2 fiber. This vector retained the increased binding and effic iency of gene transfer to well-differentiated human airway epithelia. These data suggest that inclusion of Ad17 fiber into adenovirus vectors may impr ove the outlook for gene delivery to human airway epithelia.