Structure-Property-Transfection Relationships in Polycation-mediated Non-viral DNA Delivery

Non-viral gene delivery agents, such as cationic polyelectrolytes, are attractive replacements to viruses due to the absence of potential immunogenic risk and the ability to tune their macromolecular structure. Although non-viral vectors possess numerous design advantages, several investigators have shown that transfer efficiencies are considerably lower when compared to viral vectors. The work reported in this dissertation aims to fundamentally understand the underlying structure-transfection relationships involved in polycation-mediated gene delivery. Efforts focused on the influence of molecular weight, macromolecular topology, carbohydrate modifications, and charge density on the overall transfection activity in vitro. Several families of polycations were synthesized in order to correlate chemo-physical characterization with transfection results. Results revealed that seemingly small changes in the structure of cationic polyelectrolytes can have profound consequences on their transfection activity.