Development of novel poly(ethylene glycol) based vehicles for gene therapy

Abstract

The overall goal of this project is to develop synthetic vehicles for gene therapy that facilitate intracellular delivery of DNA and enhance expression of the encoded genes. We seek to utilize expertise from the field of biomaterials to make synthetic vehicles that are less toxic, have higher transfection efficiencies, and have longer circulation times than traditional cationic polymers. Toward this goal, we have used poly (ethylene glycol) (PEG) as the backbone for our gene delivery vehicle. A difunctional PEG backbone was coupled with DNA-binding peptides (DBPs) to create a DNA condensing polymer with much lower charge ratio (+/-) than traditional cationic polymers, thus reducing the cytotoxicity of the PEG-based vehicles versus traditional cationic: polymers such as polyethylenimine (PEI) and poly-L-lysine (PLL). These DNA-binding moieties allow the PEG-based vehicles to condense DNA and self assemble into nanoparticles for gene delivery. Transfection efficiencies of these DBP-PEG vehicles were found to be comparable to other synthetic cation polymers. The self-assembling vehicles proposed above, provide a potentially non-toxic alternative to the currently available non-viral gene therapy agents.