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 2ʹ-modifications in RNAs not only evade immune activation but also suppress TLR7 and TLR8 signaling triggered by immunostimulatory RNAs. Comparable to immunosuppressive DNA oligonucleotides, 2ʹ-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 2ʹ-modified uridines.