Polyelectrolyte Complexes : Linking Chemistry and Structure to Biological Function

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Polyelectrolyte complexes are nanoparticles that form via electrostatic attraction between a polycation and polyanion. A particular class of these systems is used to introduce genetic material into cells when the polyanion is a nucleic acid sequence like DNA or RNA. We have studied these delivery systems using the polycation chitosan, a natural polymer of glucosamine that is partly acetylated, and plasmid DNA to express genes when delivered to the nucleus. We have also developed nanoparticles containing siRNA which stop expression of the target gene. Certain mechanisms by which these systems function efficiently have been elucidated using a family of custom-produced chitosans and a battery of physicochemical and structural characterization methods of the polymers and resulting nanostructures, in addition to assessment of cell uptake, intracellular trafficking and transgene expression in several cell types. This proposal aims to further elucidate the fundamental mechanisms by which effective and non-toxic delivery of nucleic acids into cells can be achieved.