Poster abstracts

Poster number 38 submitted by Sijin Guo

RNA Triangle, Square and Pentagon Nanoparticles for Potent Immunomodualtion

Sijin Guo (College of Pharmacy, Division of Pharmaceutics & Pharmaceutical Chemistry, The Ohio State University, Columbus, OH 43210, USA), Hui Li (College of Pharmacy, Division of Pharmaceutics & Pharmaceutical Chemistry, The Ohio State University, Columbus, OH 43210, USA), Daniel L. Jasinski (College of Pharmacy, Division of Pharmaceutics & Pharmaceutical Chemistry, The Ohio State University, Columbus, OH 43210, USA), Jian Fu (Center for Research on Environmental Disease, Graduate Center for Toxicology, College of Medicine, University of Kentucky, Lexington, KY 40536, USA), Yizhou Dong (College of Pharmacy, Division of Pharmaceutics & Pharmaceutical Chemistry, The Ohio State University, Columbus, OH 43210, USA), Peixuan Guo (College of Pharmacy, College of Medicine/Department of Physiology & Cell Biology, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA)

Abstract:
Modulation of immune response through cytokine induction is a vital process in vaccine development and immunology therapy. Herein, we report the development of a new generation of potent immunomodulators using RNA nanotechnology. RNA triangle, square and pentagon nanoparticles are successfully self-assembled by stretching the interior angle of thermodynamically stable 3WJ motif of phi29 bacteriophage DNA packaging motor pRNA. When immunological adjuvants were incorporated, their immunomodulation effect for cytokine TNF-alpha and IL-6 induction was greatly enhanced in vitro and in vivo, while RNA polygon controls alone induced negligible effects. The RNA nanoparticles were delivered to macrophages specifically. The degree of immunostimulation is size and shape dependent as well as the number of the payload per nanoparticles. Stronger immune response was observed as the number of adjuvants per polygon was increased. This finding demonstrates that RNA nanotechnology such as developing pRNA-based nanoparticles has the great potential to develop potent immunomodulators.

References:
[1] Khisamutdinov, E.F, Li, H, Jasinski, DL, Guo, P. (2014) Enhancing immunomodulation on innate immunity by shape transition among RNA triangle, square and pentagon nanovehicles. Nucleic Acids Res. 42:9996-10004
[2] Guo, P. (2010) The emerging field of RNA nanotechnology. Nat. Nanotechnol., 5: 833–842.
[3] Khisamutdinov EF, Jasinski DL, Guo P. (2014) RNA as a boiling-resistant anionic polymer material to build robust structures with defined shape and stoichiometry. ACS Nano, 8:4771-81.
[4] Jasinski D, Khisamutdinov EF, Lyubchenko Y, Guo P. (2014) Physicochemically Tunable Poly-Functionalized RNA Square Architecture with Fluorogenic and Ribozymatic Properties. ACS Nano. 8:7620-9.

Keywords: RNA nanotechnology, immunomodulation, CpG