Polyethylene Glycol (Molecular Weight 400 DA) Vehicle Improves Gene Expression of Adenovirus Mediated Gene Therapy

Abstract

Adenoviral gene therapy vectors suspended in PEG400 results in improved tumor control because of greater initial adenoviral spread, and the increased volume and magnitude of gene expression in vivo.

Current advances in adenovirus nanocomplexes: more specificity and less immunogenicity

“…In addition, PEG can hide the Ad capsid and thus obscure recognition by the highly expressed Ad receptors coxsackievirus and adenovirus receptor (CAR) and heparin sulphate, which are both expressed on KCs and hepatocytes (29,30), resulting in significantly augmented half-life in blood. This enhanced half-life of PEGylated Ad in the blood consequently promotes highly effective accumulation of Ad in tumor tissue via passive accumulation based on the EPR effect (24,26,31). A previously published study quantitatively analyzed the biodistribution of PEGylated Ad using a bioluminescent reporter gene visualized in a metastatic model (24).…”

“…2.1). The outer shell or distal end of PEG in Ad/polymer complexes has been conjugated with active targeting moieties such as antibodies (22), growth factors (31,(33)(34)(35)(36)(37)(38)(39), small molecular complexes of peptides (arginineglycine-aspartic acid; RGD), and ligands (27,40) in order to direct Ad to a targeted disease site (41). Direction of Ad complexes via affinity tags results in accumulation of a high concentration of Ad nanocomplexes in tumor sites, leading to highly effective gene expression.…”