Recent progress in strategies for adenovirus mediated therapeutic cell targeting

Abstract

Increasing numbers of therapeutic genes and cellular targets are available for gene therapy. Many clinical trials using virus-derived delivery systems are devoted to combat cancer, to correct single-gene malfunctions or to regenerate tissues. To develop gene delivery vectors with high efficiency through target cell selectivity, in particular under in situ conditions, remains a major challenge. The most widely used vector systems to transduce cells are based on adenoviruses. Recent approaches to develop selective adenoviral vectors (Ad) that exclusively target cells or tissues of interest without interfering with all others have focused on the modification of the broad natural tropism of adenoviruses. A popular way of Ad targeting is attained by directing vector particles towards distinct cellular receptors. Retargeting can be accomplished by linking custom-made peptides with unique specificity and reasonable affinity to cellular surface protein moieties via genetic alteration, chemical coupling or bridging with dual-specific adaptor molecules. Ideally, target-specific vectors are incapable of entering cells via their native receptors. Such altered vectors offer new opportunities to delineate functional genomics in the native environment and should enable efficient systemic therapeutic approaches. This review provides a summary of current state-of-the-art techniques to target specifically adenovirus-derived gene delivery vector systems.