Advances towards targetable adenovirus vectors for gene therapy.

Adenovirus-based vectors can efficiently transfer therapeutic genes into cells through an entry process that is initiated be binding to specific receptors on the cell surface. The receptors for the most commonly used Ad vectors include both the Coxsackie and adenovirus receptor (CAR) and omega-integrins. Therapeutic applications of AD vectors could be expanded if the specificity of gene transfer could be modulated to enhance expression of a therapeutic gene in transfer tissues and avoid non-target tissues. Ad vectors have been successfully retargeted to novel receptors using several approaches. The merits and challenges of specific approaches are discussed. In vivo evaluation of these retargeted Ad vectors has given promising results but has also highlighted additional challenges for achieving efficient targeted gene delivery. Additional modifications beyond those affecting interaction with the native receptors, CAR and integrins may be required both to avoid the clearance mechanisms that effectively remove circulating vector following systemic administration and to avoid gene transfer in non-target tissues such as the liver. Developing Ad vector that address these issues and can be targeted to novel receptors would enable gene delivery at the site of disease in applications that are currently not feasible.