Abstract
The overall objective of this project is to design a novel synthetic gene therapy vehicle with a polyethylene glycol (PEG) backbone and to use this vehicle to study the barriers to gene delivery. Current cationic polymer based synthetic vehicles, such as polyethyleneimine (PEI) and poly-L-lysine (PLL), are able to successfully condense DNA, but the efficacy of these vehicles in vitro is limited. Non-specific interactions result in low circulation half-lives and stabilities in the presence of physiological salt concentrations and serum proteins. Coupling PEG to the surface of cationic polymer vehicles has shown to improve their stability in the presence of salt and serum proteins, however the transfection efficiency of the vehicles decreased 2. We hypothesize that by using a PEG backbone modified with acrylate end groups 1 for coupling of various moieties, such as a DNA binding peptide (DBP) from the B-ZIP protein 3, we can overcome these limits. In this study, particle size, zeta potential, cytotoxicity, and transfection efficiency of PEG-based vehicles was compared with PEI and PLL-based vehicles.
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