1023. Adenoviruses Transport across a Polarized Monolayer of Caco-2 Cells by Transferrin Receptor-Mediated Transcytosis

Adenoviral (Ad) vectors are commonly used in gene delivery because they have the capacity to infect a broad range of different cell types. Recent studies have identified a 46-kDa host cell membrane protein, coxsackie-adenovirus receptor (CAR), which serves as the primary receptor for Ad serotypes 2 and 5 as well as coxsackie B virus attachment to cells. Following binding to CAR, Ad interacts with a second receptor, av integrin, which facilitates virus internalization into cells. However, significant challenges exist to the efficient use of Ad vectors for in vivo gene delivery. For example, delivery to the airway luminal surface, urothelial cells and brain remain a challenge due to the epithelial and endothelial barriers. These cells, which are joined together by complex tight intercellular junctions, form a continuous wall against the passive paracellular movement of substances. For many disorders, this is an obstacle for effective transgene delivery.