Immune regulatory oligonucleotide (IRO) compounds to modulate toll-like receptor based immune response

摘要

The invention provides novel immune regulatory oligonucleotides (IRO) as antagonist of TLRs and methods of use thereof. These IROs have unique sequences that inhibit or suppress TLR-mediated signaling in response to a TLR ligand or TLR agonist. The methods may have use in the prevention and treatment of cancer, an autoimmune disorder, airway inflammation, inflammatory disorders, infectious disease, skin disorders, allergy, asthma or a disease caused by a pathogen.

主权项

1. An immune regulatory oligonucleotide (IRO) compound comprising the sequence 5′-CTATCTGUYZTTCTCTGT-3′ (SEQ ID NO: 102), wherein G is 2′-OMe-G and U is 2′-OMe-U and wherein YZ is an oligonucleotide motif that is CpG, C*pG, C*pG* or CpG* wherein C is deoxycytosine, C* is 2′-deoxythymidine, 1-(2′-deoxy-β-D-ribofuranosyl)-2-oxo-7-deaza-8-methyl-purine, 2′-dideoxy-5-halocytosine, 2′-dideoxy-5-nitrocytosine, arabinocytidine, 2′-deoxy-5-hydroxycytidine, 2′-deoxy-N4-alkyl-cytidine, 2′-deoxy-4-thiouridine, or other pyrimidine nucleoside analogs; G is deoxyguanosine, and G* is 2′-deoxy-7-deazaguanosine, 2′-deoxy-6-thioguanosine, arabinoguanosine, 2′-deoxyinosine, or other purine nucleoside analogs.