Adenoviruses are efficient vehicles for transducing airway epithelial cells. Human adenoviruses (Ads) are classified into seven species termed A-G. Most species use the coxsackie-adenovirus receptor (CAR) as a primary cellular receptor. Ad group B is notable because it is further divided into groups B1 and B2 and its members use CD46 or desmoglein 2 (DSG2) as cellular receptors. To date, human Ad types 2 and 5 have been the predominant choices for preclinical and clinical trials using Ad-based viral vectors in the airways. In this study, we screened 14 Ad types representing species C, B1, B2, D, and E. Using well-differentiated primary cultures of human airway epithelial cells (HAEs), we examined transduction efficiency. Based on GFP or nanoluciferase expression, multiple Ad types transduced HAEs as well as or better than Ad5. Ad3, Ad21, and Ad14 belong to species B and had notable transduction properties. We further examined the transduction properties of conditionally reprogrammed airway basal cells and primary basal cells from human lung donors. Again, the transduction efficiency of species B members outperformed the other types. These data suggest that adenoviral vectors based on species B transduce fully differentiated epithelial cells and progenitor cells in the human airways better than Ad5.
Keywords: CD46; coxsackie-adenovirus receptor; desmoglein 2; gene therapy; lung gene transfer; respiratory system.