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 a therapeutic agent to "shield" or reduce interactions of it with proteins and cells that would normally decrease the therapeutics' interactions with its target.
PEG has also been applied to improve the pharmacology of adenoviral (Ad) vectors. Previous work has demonstrated that PEG could protect Ad vectors from pre-existing neutralizing antibodies to allow multiple administration into immune recipients. PEGylation also reduces the production of new antibody and cellular immune responses against Ad.
The Virology, Vector and Vaccine Engineering Lab has demonstrated PEG's ability to reduce the problematic innate immune responses provoked by Ad vectors in vivo in reducing the nonspecific 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.