Poster abstracts

Poster number 127 submitted by Jake Durbin

Structure and Composition Define Immunorecognition of Nucleic Acid Nanoparticles.

Emil F. Khisamutdinov (Chemistry, Ball State University), Jake K. Durbin (Biology, Ball State University), Nathan McCann (Chemistry, Ball State University), E. Hong (Chemistry, Ball State University), JR Halman (Chemistry, Ball State University)

Abstract:

Nucleic acid nanoparticles (NANPs) have evolved as a new class of therapeutics that could potentially be used in immunomodulation therapy to treat diseases by enhancing, inducing, or suppressing an immune response that would be beneficial to the host. Despite tremendous advancements in NANP development, their immunotoxicity has never been fully characterized. Here, we describe a systematically studied immunological recognition of representative RNA and DNA NANPs selected to have different design principles and physicochemical properties. We discover that, unlike traditional TNAs, NANPs used without a delivery carrier are immunoquiescent. We show that interferons (IFNs) are the key cytokines triggered by NANPs after their internalization by phagocytic cells. However, in addition to type I IFNs, type III IFNs also serve as reliable biomarkers of NANPs, which is usually not characteristic of TNAs. We show that overall immunostimulation relies on the NANP's shape, connectivity, and composition. We demonstrate that, like with traditional TNAs, plasmacytoid dendritic cells serve as the primary interferon producers among all peripheral blood mononuclear cells treated with NANPs, and scavenger receptor-mediated uptake and endosomal Toll-like receptor signaling are essential for NANP immunorecognition. The TLR involvement, however, is different from that expected for traditional TNA recognition. Based on these results, we suggest that NANP technology may serve as a prototype of auxiliary molecular language for communication with the immune system and the modulation of immune responses.

Keywords: RNA and DNA nanoparticles, immunorecognition, interferons