MEDI 108 |
| Single-stranded viral RNAs have been shown as ligands for Toll-like receptor (TLR) 7 and/or TLR8. Previously we have designed novel structures of single-stranded oligoribonucleotides (ORN) containing two 5'-ends. These novel ORN, referred to as Stabilized Immune Modulatory RNA (SIMRA), are stable against nucleases and acted as agonists of TLR8 and 7. In the present study, we have designed and synthesized several ORN sequences with the ability to form intermolecular duplexes. Such novel ORN are more stable against nucleases because of the secondary structure. The new ORN that form secondary structures activated HEK293 cells expressing human TLR8, but not human TLR3 that is receptor for double-stranded RNA. The new ORN showed potent induction of cytokines and chemokines in human cell-based assays. The ORN that can form secondary structures are a novel class of TLR8 ligands. |
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Poster Session
7:00 PM-9:00 PM, Sunday, August 19, 2007 BCEC -- Exhibit Hall - B2, Poster
Division of Medicinal Chemistry |