Modification of adenovirus gene transfer vectors with synthetic polymers: a scientific review and technical guide

The chemical modification of adenovirus (Ad) gene transfer vectors with synthetic polymers is a promising strategy for overcoming typical in vivo hurdles associated with Ad-mediated gene delivery. Polymer-modified Ad vectors induce significantly reduced innate immune responses, can evade pre-existing anti-Ad antibodies, allow for repeated vector delivery, and have been used for developing novel retargeting strategies. The most widely used polymers for covalent chemical capsid surface modification are poly-N-(2-hydroxypropyl)methacrylamide (poly-HPMA) and polyethylene glycol (PEG), and the latter is in wide clinical use for modifying protein biopharmaceuticals. In this review, we critically compare the properties of various polymers with respect to Ad vector shielding and retargeting, and identify areas for future research on polymer-modified viral vectors. We describe the potential technical pitfalls of polymer modification of Ad vectors and provide a technical guide for avoiding these while establishing polymer modification techniques in the laboratory.