Development of TLR7/8 small RNA antagonists.
Toll-like receptors (TLRs) expressed by innate immune cells recognize a spectrum of microbial structures. Recent studies have provided convincing evidence that TLR7 and TLR8 play a key role in sensing viral RNAs. Under certain conditions these receptors can also recognize self-RNA leading to the induction and/or perpetuation of autoimmune diseases. Recently, we have shown that the incorporation of 2'-modifications in RNAs not only evade immune activation but also suppress TLR7 and TLR8 signaling triggered by immunostimulatory RNAs. Comparable to immunosuppressive DNA oligonucleotides, 2'-modified RNAs may have utility as inhibitors of pathogenic inflammatory reactions mediated by TLR activation. This chapter describes the characterization of immunosuppressive RNA oligonucleotides carrying 2'-modified uridines.
Sioud
Mouldy
M
Department of Immunology, Institute for Cancer Research, Rikshospitalet-Radiumhospitalet, University Hospital, Oslo, Norway.
D000328:Adult; D001483:Base Sequence; D002469:Cell Separation; D004797:Enzyme-Linked Immunosorbent Assay; D005229:Fatty Acids, Monounsaturated / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007114:Immunization; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008967:Molecular Biology / Q000379:methods*; D008969:Molecular Sequence Data; D009841:Oligonucleotides / Q000235:genetics; D000644:Quaternary Ammonium Compounds / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism*; D051199:Toll-Like Receptor 7 / Q000037:antagonists & inhibitors*; D051200:Toll-Like Receptor 8 / Q000037:antagonists & inhibitors*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D005229:Fatty Acids, Monounsaturated; D009841:Oligonucleotides; D000644:Quaternary Ammonium Compounds; D034741:RNA, Small Interfering; D051199:Toll-Like Receptor 7; D051200:Toll-Like Receptor 8; D014409:Tumor Necrosis Factor-alpha; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane