Abstract: The events of the COVID-19 pandemic have accelerated developments into mRNA therapies and research into novel mRNA delivery vehicles. While lipid-based nanoparticles have gained prominence, polymeric nanoparticle vehicles remain promising biodegradable vectors for new therapeutic RNAs. Within this dissertation two convergent approaches to polydisulfide polymer synthesis are explored. Utilizing a two-step post-polymerization functionalization strategy, multifunctional polydisulfide polymers were generated with motifs essential for mRNA complexation and endosomal escape in cells. Successful delivery of a model vaccine mRNA to dendritic cells highlights the utility of this design approach and future applications of these polymers. Poly(anionic/cationic)disulfides were also generated from a facile "cryopolymerization" approach, using frozen aqueous conditions to favor ring-opening polymerization of monomers. Resulting polydisulfides also demonstrate promise as RNA delivery vehicles. Additionally, in vitro CRISPR-Cas9 gene editing was explored using polymeric nanoparticles formed from cationic dendronized polymers and relevant RNA molecules.
Thursday, November 10, 2022 - 3:00pm
James Collin Hickey