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dc.contributor.authorHess, K.L.
dc.contributor.authorAndorko, J.I.
dc.contributor.authorTostanoski, L.H.
dc.date.accessioned2019-10-08T19:43:53Z
dc.date.available2019-10-08T19:43:53Z
dc.date.issued2017
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85002836321&doi=10.1016%2fj.biomaterials.2016.11.052&partnerID=40&md5=a8790d2c7ce9bdd9ff583dc60bf2a5a0
dc.identifier.urihttp://hdl.handle.net/10713/11128
dc.description.abstractAutoimmune diseases occur when the immune system incorrectly recognizes self-molecules as foreign; in the case of multiple sclerosis (MS), myelin is attacked. Intriguingly, new studies reveal toll-like receptors (TLRs), pathways usually involved in generating immune responses against pathogens, play a significant role in driving autoimmune disease in both humans and animal models. We reasoned polyplexes formed from myelin self-antigen and regulatory TLR antagonists might limit TLR signaling during differentiation of myelin-specific T cells, inducing tolerance by biasing T cells away from inflammatory phenotypes. Complexes were formed by modifying myelin peptide with cationic amino acids to create peptides able to condense the anionic nucleic-acid based TLR antagonist. These immunological polyplexes eliminate synthetic polymers commonly used to condense polyplexes and do not rely on gene expression; however, the complexes mimic key features of traditional polyplexes such as tunable loading and co-delivery. Using these materials and classic polyplex analysis techniques, we demonstrate condensation of both immune signals, protection from enzymatic degradation, and tunable physicochemical properties. We show polyplexes reduce TLR signaling, and in primary dendritic cell and T cell co-culture, reduce myelin-driven inflammation. During mouse models of MS, these tolerogenic polyplexes improve the progression, severity, and incidence of disease. Copyright 2016 The Authorsen_US
dc.description.sponsorshipThis work was supported in part by the National Multiple Sclerosis Society Award # RG-1501-02968 and # PP2103, NSF CAREER Award # 1351688, and the University of Maryland Venture Fund. K.LH. is a SMART Graduate Fellow funded by ASD/R&E , Defense-Wide/ PE0601120D8Z National Defense Education Program (NDEP)/BA-1, Basic Research.en_US
dc.description.urihttps://doi.org/10.1016/j.biomaterials.2016.11.052en_US
dc.language.isoen_USen_US
dc.publisherElsevier Ltden_US
dc.relation.ispartofBiomaterials
dc.subjectImmunologyen_US
dc.subjectNanoparticleen_US
dc.subjectPolyplexen_US
dc.subjectSelf-assemblyen_US
dc.subjectTolerance and autoimmunityen_US
dc.subjectToll-like receptoren_US
dc.titlePolyplexes assembled from self-peptides and regulatory nucleic acids blunt toll-like receptor signaling to combat autoimmunityen_US
dc.typeArticleen_US
dc.identifier.doi10.1016/j.biomaterials.2016.11.052
dc.identifier.pmid27940382


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