Poster abstracts

Poster number 43 submitted by Sijin Guo

RNA triangle, square and pentagon nanoparticles for potent immunomodulation

Sijin Guo (Department of Chemistry, Nanobiotechnology Center, University of Kentucky), Hui Li (Department of Pharmaceutical Sciences, College of Pharmacy, Markey Cancer Center, Nanobiotechnology Center, University of Kentucky), Daniel L. Jasinski (Department of Pharmaceutical Sciences, College of Pharmacy, Markey Cancer Center, Nanobiotechnology Center, University of Kentucky), Jiao Chen (Center for Research on Environmental Disease, Graduate Center for Toxicology, College of Medicine, University of Kentucky), Jian Fu (Center for Research on Environmental Disease, Graduate Center for Toxicology, College of Medicine, University of Kentucky), Peixuan Guo (Department of Pharmaceutical Sciences, College of Pharmacy, Markey Cancer Center, Nanobiotechnology Center, University of Kentucky)

Abstract:
Modulation of immune response through cytokine induction is a vital process in vaccine development and immunology therapy. Herein, we reported 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 induced unnoticeable effect. 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 RNA nanoparticles based on pRNA has the great potential to develop potent immunomodulators.

References:
[1] Guo,P. (2010) The emerging field of RNA nanotechnology. Nat. Nanotechnol., 5, 833–842.
[2] Khisamutdinov,E.F., Jasinski,D.L. and Guo,P. (2014) RNA as a boiling-resistant anionic polymer material to build robust structures with defined shape and stoichiometry. ACS Nano,8, 4771–4781.
[3] Jasinski,D.L., Khisamutdinov,E.F., Lyubchenko,Y. and Guo,P. (2014) Physicochemically Tunable Poly-Functionalized RNA Square Architecturewith Fluorogenic and Ribozymatic Properties. ACS Nano, doi:10.1021/nn502160s .

Keywords: immunomodulation, RNA polygon, 3WJ