Tailorable, non-toxic, PEI-based, nucleic acid delivery systems have been synthesized by covalent modification of the cationic polymer backbone. The modular approach used to prepare these non-viral vectors enables the insertion of controlled amounts of fluorescent labels, toxicity mitigators and cell targeting moieties. This work describes the toxicity and transfection ability of a pair of novel, chemically-related, polymers in three different mammalian cell lines. Fluorescently-tagged polymer and fluorescently-labeled plasmid DNA were used to enable the detailed monitoring of the location and shape evolution of the DNA-delivering complexes within cells via confocal microscopy. Our studies demonstrate that minor differences in the chemical architecture of the functionalized PEIs can have significant effects on cell toxicity, and polymer-DNA aggregate size/charge ratios. The use of fluorescent labels in both plasmid DNA and cationic polymer produced fundamental insights into the effect of polymer structure on its interaction with the polynucleotides and the cell membrane. A better understanding of these interactions will enable the identification of promising pathways towards the development of effective, targeted cationic polymer-based reagents.

Modular non-viral gene delivery vectors as probes to study the evolution of DNA-polymer complexes within mammalian cells

2019 Spring National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.