Poster abstracts

Poster number 9 submitted by Morgan Chandler

Cationic amphiphilic co-polymers as carriers of RNA nanoparticles for controlled gene silencing, immunostimulation, and biodistribution

Morgan Chandler (Department of Chemistry, University of North Carolina at Charlotte), Justin R. Halman, Lauren Rackley, M. Brittany Johnson, Ian Marriott (Department of Chemistry, Department of Biology, University of North Carolina at Charlotte), Ki-Taek Kim, So-Jung Gwak, Richard Pace (Department of Bioengineering, Clemson University), Mathias Viard (Cancer and Inflammation Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research), Jeoung Soo Lee (Department of Bioengineering, Clemson University), Kirill A. Afonin (Department of Chemistry, University of North Carolina at Charlotte)

Abstract:
The programmed assembly of RNA nanoparticles provides a means for the controlled coordination of therapeutic moieties on a biocompatible scaffold. While the delivery of nucleic acids in general remains a challenge, new candidates to serve as carriers are emerging and are continuously tested. Polymeric platforms have proven to be promising for clinical translation, as they are efficient in shielding nucleic acid cargos from nuclease degradation while still promoting their delivery and intracellular release. In this work, we combine the stable cationic poly-(lactide-co-glycolide)-graft-polyethylenimine, known as the carrier PgP, with functionalized RNA nanoparticles. We compare several representative nanostructure designs of different connectivity and dimensionality, including cubic, ring, and fibrous RNA nanoparticles, to assess how overall structure influences delivery with the same carrier. As a result, the extensive study of these formulations both in vitro and in vivo reveals nanoparticle-dependent differences in their immunostimulatory activity, gene silencing efficiency, and biodistribution.

References:
Halman, J. R.; Kim, K.-T.; Gwak, S.-J.; Pace, R.; Johnson, M. B.; Chandler, M. R.; Rackley, L.; Viard, M.; Marriott, I.; Lee, J. S.; Afonin, K. A., A cationic amphiphilic co-polymer as a carrier of nucleic acid nanoparticles (NANPs) for controlled gene silencing, immunostimulation, and biodistribution. Nanomedicine: Nanotechnology, Biology and Medicine 2020, 23, 102094.

Keywords: nanoparticle, carrier, immunostimulation