Polymer Shielding of Vectors and Vaccines
Polyethylene glycol (PEG) is a clinically-approved conjugation agent used to improve the pharmacokinetics of a variety of protein therapeutics. In these applications, the hydrophilic PEG molecule is cross-linked to the therapeutic agent to “shield” or reduce interactions of it with proteins and cells that would normally decrease the therapeutic’s interactions with its target. PEG has also been applied to improve the pharmacology of Ad vectors. Previous work demonstrated that PEG could protect Ad from pre-existing neutralizing antibodies to allow multiple administration into immune recipients (3, 56-58). PEGylation also reduces the production of new antibody and cellular immune responses against Ad (3). We have demonstrated PEG’s ability to reduce the problematic innate immune responses provoked by Ad in vivo (Molecular Therapy 11(1):66-79 2005) and in reducing the non-specific interactions of the virus with blood cells and endothelium. Work is underway to test PEG and other polymers for their shielding and protective functions for liver gene therapy, cancer therapy, and during vaccination.