Modulation of Endosomal Toll-Like Receptor-Mediated Immune Responses by Synthetic Oligonucleotides
Identifieur interne : 002540 ( Main/Exploration ); précédent : 002539; suivant : 002541Modulation of Endosomal Toll-Like Receptor-Mediated Immune Responses by Synthetic Oligonucleotides
Auteurs : Ekambar R. Kandimalla [États-Unis] ; Sudhir Agrawal [États-Unis]Source :
- Advances in Polymer Science [ 0065-3195 ]
Abstract
Abstract: Toll-like receptors (TLRs) 7, 8, and 9 belong to a family of endosomal receptors that are known to detect pathogen-associated nucleic acid molecular patterns and induce appropriate immune responses. Viral single-stranded RNA is the ligand for TLR7 and TLR8, and bacterial and viral DNA containing unmethylated CpG motifs is the ligand for TLR9. We have extensively studied the structure–activity relationships of synthetic oligonucleotides towards the goal of creating novel agonists of TLRs 7, 8, and 9 to modulate immune responses mediated through targeted receptors. Agonists of TLRs 7, 8, and 9 are being studied as therapeutic agents for various diseases, including cancers, allergies, asthma, and infectious diseases, and also as adjuvants with vaccines. In addition, under certain pathological conditions, TLR7 and TLR9 are shown to recognize immune complexes containing self-nucleic acids and contribute to the progression of autoimmune diseases, including lupus, arthritis, psoriasis, and multiple sclerosis. Using the insights gained by studying the interactions of oligonucleotides with endosomal TLRs, we have created oligonucleotide-based antagonists that inhibit both TLR7- and TLR9-mediated immune responses for the treatment of autoimmune and inflammatory diseases. Out of the large portfolio of oligonucleotide-based TLR agonists and antagonists designed, four candidates are currently being evaluated in clinical trials for a broad range of disease indications.
Url:
DOI: 10.1007/12_2011_138
Affiliations:
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