Barriers to vector-mediated gene transfer in WD columnar airway epithelial cells. The failure of vectors to bind to the apical membrane of WD cells is depicted on the left cell; the failure of “non-specifically” bound vectors to internalize is shown on the right cell. The tight junctions separate the apical cell membrane from the basolateral domain that selectively expresses specific viral receptors, e.g., the CAR, “housekeeping”/growth receptors, and integrins. WD, well-differentiated. CAR, Coxsackie virus and adenovirus receptor.