title: Immunostimulating capacities of stabilized RNA molecules.
abstract: Since direct injection of naked mRNA induces an immune response, we tested the capacity of RNA to signal danger. We show here that mRNA molecules that are protected from immediate degradation either through interaction with cationic proteins (trans protection) or through chemical modification of the phosphodiester backbone (phosphorothioate RNA; cis protection) act as sequence-independent danger signals on mouse DC. As opposed to CpG DNA, the cis-stabilized RNA is degraded in a few minutes, does not activate B cells and, in contrast to double-stranded RNA, requires MyD88 for activation of the DC. We postulate that phosphorothioate RNA, which mimics trans-stabilized RNA, is a new PAMP.
authors.affiliation: CureVac GmbH, Tübingen, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Scheel
authors.forename: Sybilla
authors.initials: S
authors.lastname: Braedel
authors.forename: Jochen
authors.initials: J
authors.lastname: Probst
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Carralot
authors.forename: Hermann
authors.initials: H
authors.lastname: Wagner
authors.forename: Hansjorg
authors.initials: H
authors.lastname: Schild
authors.forename: Günther
authors.initials: G
authors.lastname: Jung
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Rammensee
authors.forename: Steve
authors.initials: S
authors.lastname: Pascolo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000276:Adjuvants, Immunologic / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D000943:Antigens, Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D007114:Immunization; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013873:Thionucleotides / Q000276:immunology / Q000494:pharmacology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D000943:Antigens, Differentiation; D015850:Interleukin-6; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D013873:Thionucleotides; D018664:Interleukin-12