Exploring the Functions of Polymers in Adenovirus-Mediated Gene Delivery: Evading Immune Response and Redirect Tropism

Abstract

Adenoviruses (Ads) are promising viral carriers for gene therapy because of their unique attribution. However, clinical applications of Ad vectors are currently restricted by their immunogenicity and broad native tropism. To address these obstacles, a variety of non-immunogenic polymers are utilized to modify Ad vectors chemically or physically. In this review, we systemically discuss the functions of polymers in Ad-mediated gene delivery from two aspects, evading the host immune responses to Ads and redirecting Ad tropism. With polyethylene glycol (PEG) first in order, a variety of polymers have been developed to shield the surface of Ad vectors, and well accomplished to evade the host immune response, block CAR-dependant cellular uptake and reduce liver accumulation. Besides these functions, shielding Ad vectors with targeted polymers (including targeting ligands conjugated polymers and bio-responsive polymers) can also efficiently retarget Ad vectors to tumor tissues and reduce their distribution at non-targeted tissues. With its potentials to evade the immune response and retarget Ad vectors, modification with polymers has been generally regarded as a promising strategy to facilitate the clinical applications of Ad vectors for virotherapy.