Fig. 1. Physical and physiological barriers to viral vector mediated airway gene transfer.

The airway epithelium consists of multiple barriers that limit the ability of viral vectors to deliver their transgene to the target cells. Barriers include surface mucus and the action of the mucociliary clearance (MCC); lack of relevant viral vector receptors on the apical membrane; epithelial tight junctions that prevent vector particles accessing basolateral-located receptors; and the deep-lying location of basal stem cells that are not easily accessible via the airway lumen. PCL periciliary liquid, ASL airway surface layer.