Methods and compositions for inhibition of innate immune responses and autoimmunity

Abstract

The invention provides immunoregulatory polynucleotides and methods for immunoregulation of individuals using the immunoregulatory polynucleotides.

1 - 43 . (canceled) 
     
     
         44 . A method of inhibiting a TLR7/8 dependent and/or a TLR9 dependent immune response in a human, the method comprising administering to the human a composition comprising an oligonucleotide in an amount sufficient to inhibit the TLR7/8 dependent and/or TLR9 dependent immune response in said human, wherein the oligonucleotide comprises SEQ ID NO: 52 or an analog of SEQ ID NO: 52, the oligonucleotide is less than 50 bases or base pairs and does not comprise a CG dinucleotide, and wherein in the analog of SEQ ID NO: 52 one principal base is replaced with a naturally occurring base or a modified, non-naturally occurring base. 
     
     
         45 . The method of  claim 44  for inhibiting a TLR7/8 dependent immune response. 
     
     
         46 . The method of  claim 44  for inhibiting a TLR9 dependent immune response. 
     
     
         47 . The method of  claim 44  for inhibiting a TLR7/8 dependent and a TLR9 dependent immune response. 
     
     
         48 . The method of  claim 44 , wherein the inhibiting comprises suppressing TLR7/8 dependent and/or TLR9 dependent cytokine production in the human. 
     
     
         49 . The method of  claim 44 , wherein the oligonucleotide comprises a 5′-GGGG-3′ sequence. 
     
     
         50 . The method of  claim 44 , wherein the oligonucleotide comprises a 5′-TGC-3′ sequence at the 5′ end of the oligonucleotide. 
     
     
         51 . The method of  claim 44 , wherein the oligonucleotide comprises SEQ ID NO:52. 
     
     
         52 . The method of  claim 44 , wherein the oligonucleotide comprises an analog of SEQ ID NO: 52. 
     
     
         53 . The method of  claim 44 , wherein the oligonucleotide contains phosphate-modified linkages. 
     
     
         54 . The method of  claim 53 , wherein the oligonucleotide contains only phosphorothioate linkages. 
     
     
         55 . The method of  claim 44 , wherein the oligonucleotide is less than 40 bases or base pairs in length. 
     
     
         56 . The method of  claim 55 , wherein the oligonucleotide is less than 30 bases or base pairs in length. 
     
     
         57 . The method of  claim 55 , wherein the oligonucleotide is less than 25 bases or base pairs in length. 
     
     
         58 . The method of  claim 55 , wherein the oligonucleotide is less than 20 bases or base pairs in length. 
     
     
         59 . The method of  claim 44 , wherein the oligonucleotide is single-stranded. 
     
     
         60 . The method of  claim 44 , wherein the oligonucleotide is double-stranded. 
     
     
         61 . The method of  claim 44 , wherein the composition is a pharmaceutical composition comprising a pharmaceutically acceptable excipient. 
     
     
         62 . The method of  claim 61 , wherein the pharmaceutical composition comprises a sterile, isotonic solution. 
     
     
         63 . A pharmaceutical composition comprising an oligonucleotide and a pharmaceutically acceptable excipient, wherein the oligonucleotide comprises SEQ ID NO: 52 or an analog of SEQ ID NO: 52, the oligonucleotide is less than 50 bases or base pairs in length and does not comprise a CG dinucleotide, and wherein in the analog of SEQ ID NO: 52 one principal base is replaced with a naturally occurring base or a modified, non-naturally occurring base.