Immunomodulatory nucleic acid nanoparticles (NANPs) stimulate protective bone cell responses following S. aureus challenge.
Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B618
Abstract ID: 5578
Presenting Author:
Erin Mills , PhD Student at Univ. of North Carolina, Charlotte
Abstract:
Staphylococcal osteomyelitis remains difficult to treat due to the emergence of antibiotic-resistant strains and the ability of Staphylococcus aureus to persist intracellularly. This necessitates the development of new treatment options. The use of nucleic acid-based nanoparticles (NANPs) is an attractive new approach to combat such infections as they are versatile scaffolds that can be rationally designed to self-assemble into planar or 3-dimensional shapes. Importantly, NANPs can be engineered to be immunomodulatory based upon the incorporation of motifs that are recognized by pattern recognition receptors. Here, we demonstrate the delivery of four structurally dissimilar NANPs, DNA cubes, RNA cubes, rings, and fibers, into primary murine osteoblasts and osteoclasts, two resident bone cell types that play critical roles in osteomyelitis-associated bone loss. Of these, we show that DNA and RNA cubes are immunostimulatory and initiate production of type I interferons via the cytosolic nucleic acid sensors, cGAS and RIG-I, in the absence of effects on bone homeostatic mediator expression. Interestingly, we have shown that DNA cube-mediated type I interferon production can significantly reduce intracellular bacterial burden in vitro, and can elevate IFN-β levels in infected murine femurs following in vivo administration. These exciting findings support the development of this technology as a new therapeutic strategy for osteomyelitis.
Immunomodulatory nucleic acid nanoparticles (NANPs) stimulate protective bone cell responses following S. aureus challenge.
Category
Poster and Podium (Block Symposium)