Adeno-associated virus type 5 (AAV5) but not AAV2 binds to the apical surfaces of airway epithelia and facilitates gene transfer

In the genetic disease cystic fibrosis, recombinant adeno-associated virus type 2 (AAV2) is being investigated as a vector to transfer CFTR cDNA to ai rway epithelia. However, earlier work has shown that the apical surface of human airway epithelia is resistant to infection by AAV2, presumably as a r esult of a lack of heparan sulfate proteoglycans on the apical surface. Thi s inefficiency can be overcome by increasing the amount of vector or by inc reasing the incubation time. However, these interventions are not very prac tical for translation into a therapeutic airway-directed vector. Therefore, ,ve examined the efficiency of other AAV serotypes at infecting human airwa y epithelia. When applied at low multiplicity of infection to the apical su rface of differentiated airway epithelia we found that a recombinant AAV5 b ound and mediated gene transfer 50-fold more efficiently than AAV2. Further more, in contrast to AAV2, AAV5-mediated gene transfer was not inhibited by soluble heparin. Recombinant AAV5 was also more efficient than AAV2 in tra nsferring beta-galactosidase cDNA to murine airway and alveolar epithelia i n vivo. These data suggest that AAV5-derived vectors bind and mediate gene transfer to human and murine airway epithelia, and the tropism of AAV5 may be useful to target cells that are not permissive for AAV2.