Peptide-Based Technologies to Alter Adenoviral Vector Tropism: Ways and Means for Systemic Treatment of Cancer

Abstract

Due to the fundamental progress in elucidating the molecular mechanisms of human diseases and the arrival of the post-genomic era, increasing numbers of therapeutic genes and cellular targets are available for gene therapy. Meanwhile, the most important challenge is to develop gene delivery vectors with high efficiency through target cell selectivity, in particular under in situ conditions. The most widely used vector system to transduce cells is based on adenovirus (Ad). Recent endeavors in the development of selective Ad vectors that target cells or tissues of interest and spare the alteration of all others have focused on the modification of the virus broad natural tropism. A popular way of Ad targeting is achieved by directing the vector towards distinct cellular receptors. Redirecting can be accomplished by linking custom-made peptides with specific affinity to cellular surface proteins via genetic integration, chemical coupling or bridging with dual-specific adapter molecules. Ideally, targeted vectors are incapable of entering cells via their native receptors. Such altered vectors offer new opportunities to delineate functional genomics in a natural environment and may enable efficient systemic therapeutic approaches. This review provides a summary of current state-of-the-art techniques to specifically target adenovirus-based gene delivery vectors.

Stimulation of Innate Immunity byIn VivoCyclic di-GMP Synthesis Using Adenovirus

“…Miyabe et al (20) showed that enhancing c-di-GMP entry into cancer cells using liposomes increased its efficacy; adenovirus delivery of DGCs to tumors might function similarly by driving synthesis of c-di-GMP in cancer cells. One advantage of using adenovirus over general administration for this purpose is that modified adenovirus vectors have been constructed to target specific tissue types (66), and c-di-GMP might be directly delivered to tumor cells or other tissues.…”

Oncolytic Adenoviruses: Strategies for Improved Targeting and Specificity

“…Similar to hexon-based studies, keeping the structural stability in mind, small peptides are widely used. However, proteins as large as 83 amino acids have been introduced into this domain, but the viral packaging was somewhat affected [87,88,98,99]. Therefore, smaller proteins and peptides seem to be the better options.…”

Novel subventricular zone early progenitor cell-specific adenovirus for in vivo therapy of central nervous system disorders reinforces brain stem cell heterogeneity

“…Due to the abundance of CAR in many tissues, adenoviruses naturally display a broad tropism and infect a wide spectrum of cells (Chailertvanitkul and Pouton 2010;Waehler et al 2007). Thus, the most important challenge is to develop Ad-derived gene delivery systems with high efficiency through target cell selectivity, in particular under in situ conditions (Reetz et al 2014). Our recent endeavors in the generation of Ad vectors that specifically target stem/progenitor cells in the body have focused on linking selective peptides to viral particles that direct the virus to specific or yet unknown receptors on the surface of stem cells (Hildebrandt et al 2010;Schmidt et al 2007).…”