Poster abstracts
Poster number 16 submitted by Sijin Guo
Size, shape, and sequence-dependent of immunogenicity of RNA nanoparticles
Sijin Guo (Center for RNA Nanobiotechnology and Nanomedicine; College of Pharmacy, Division of Pharmaceutics and Pharmaceutical Chemistry; The Ohio State University, Columbus, OH 43210, USA), Hui Li (Center for RNA Nanobiotechnology and Nanomedicine; College of Pharmacy, Division of Pharmaceutics and Pharmaceutical Chemistry; The Ohio State University, Columbus, OH 43210, USA), Mengshi Ma (Center for Research on Environmental Disease; College of Medicine, Department of Toxicology and Cancer Biology; University of Kentucky, Lexington, KY 40506, USA), Jian Fu (Center for Research on Environmental Disease; College of Medicine, Department of Toxicology and Cancer Biology; University of Kentucky, Lexington, KY 40506, USA), Yizhou Dong (Center for RNA Nanobiotechnology and Nanomedicine; College of Pharmacy, Division of Pharmaceutics and Pharmaceutical Chemistry; The Ohio State University, Columbus, OH 43210, USA), Peixuan Guo (Center for RNA Nanobiotechnology and Nanomedicine; College of Pharmacy; College of Medicine; Dorothy M. Davis Heart and Lung Research Institute; NCI Comprehensive Cancer; The Ohio State University)
Abstract:
RNA molecules have emerged as promising therapeutics. Like all other drugs, the safety profile and immune response are important criteria for drug evaluation. However, literatures on RNA immunogenicity have been controversial. Here, we used the approach of RNA nanotechnology to demonstrate the immune response of RNA nanoparticles is size, shape, and sequence-dependent. RNA triangle, square, pentagon and tetrahedron with same shape but different sizes, or same size but different shapes were used as models to investigate the immune response. The levels of pro-inflammatory cytokines induced by these RNA nanoarchitectures were assessed in macrophage-like cells and animals. It was found that RNA polygons without extension at the vertexes were immune-inert. However, when single-stranded RNA with a specific sequence was extended from the vertexes of RNA polygons, strong immune responses were detected. These immunostimulations are sequence-specific, since some other extended sequences induced little or no immune response. Additionally, larger size RNA square induced stronger cytokine secretion. 3D RNA tetrahedron showed stronger immunostimulation than planar triangular RNA. These results suggest that the immunogenicity of RNA nanoparticles is tunable to produce either a minimal immune response that can serve as safe therapeutic vectors, or a strong immune response for cancer immunotherapy or vaccine adjuvants.
References:
Guo S, Li H, Ma M, Fu J, Dong Y, Guo P. Size, Shape and Sequence-dependent Immunogenicity of RNA Nanoparticles. Mol Ther Nucleic Acids. 2017 Dec; 9:399-408.
Keywords: RNA nanotechnology, RNA nanoparticle, RNA nanostructure