Integrin-Targeting Strategies for Adenovirus Gene Therapy

Numerous human adenovirus (AdV) types are endowed with arginine-glycine-aspartic acid (RGD) sequences that enable them to recognize vitronectin-binding (alpha v) integrins. These RGD-binding cell receptors mediate AdV entry into host cells, a crucial early step in virus infection. Integrin interactions with adenoviruses not only initiate receptor-mediated endocytosis but also facilitate AdV capsid disassembly, a prerequisite for membrane penetration by AdV protein VI. This review discusses fundamental aspects of AdV-host interactions mediated by integrins. Recent efforts to re-engineer AdV vectors and non-viral nanoparticles to target alpha v integrins for bioimaging and the eradication of cancer cells will also be discussed.