Compositions and Methods for Inducing an Immune Response in a Mammal and Methods of Avoiding an Immune Response to Oligonucleotide Agents Such as Short Interfering RNAs

Abstract

Tis invention provides oligonucleotide agents that modulate an immune response by stimulating IFN production and methods of using such agents for therapeutic treatments of mammals.

1 . A method of stimulating an immune response in a mammal comprising administering to said mammal an RNA oligonucleotide agent comprising a sequence of 4 or more, 5 or more, 6 or more, 7 or more or 8 or more contiguous nucleotides from SEQ ID NO:1, taken from the 5′ end of this sequence, wherein the agent is at least 12 nucleotides in length. 
     
     
         2 . The method of  claim 1 , wherein the oligonucleotide agent comprises SEQ ID NO:1, or a sequence that differs by not more than 1 or not more than 2 nucleotides from SEQ ID NO: 1. 
     
     
         3 . The method of  claim 1 , wherein the oligonucleotide agent comprises at least two repeats of SEQ ID NO:1. 
     
     
         4 . The method of  claim 1 , wherein said sequence is chosen from the group of SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6. 
     
     
         5 . The method of  claim 1 , wherein the oligonucleotide agent is an iRNA agent. 
     
     
         6 . The method of  claim 1 , wherein said agent is a single stranded RNA agent. 
     
     
         7 . A method of making an oligonucleotide agent so as to avoid stimulating an immune response in a mammal comprising eliminating from a potential agent pool any agent that comprises a sequence of 4 or more, 5 or more, 6 or more, 7 or more or 8 or more contiguous nucleotides from SEQ ID NO:1, taken from the 5′ end of this sequence, or a sequence that differs from SEQ ID NO:1 by not more than one or not more than 2 nucleotides. 
     
     
         8 . The method of  claim 7 , wherein the oligonucleotide agent is an iRNA agent. 
     
     
         9 . The method of  claim 7 , wherein said agent is a single stranded RNA agent. 
     
     
         10 . An isolated oligonucleotide agent for inducing an immune response comprising a sequence of 4 or more, 5 or more, 6 or more, 7 or more or 8 or more contiguous nucleotides from SEQ ID NO:1, taken from the 5′ end of this sequence, wherein the agent is at least 12 nucleotides in length. 
     
     
         11 . The isolated oligonucleotide agent of  claim 10 , wherein the oligonucleotide agent comprises SEQ ID NO:1, or a sequence that differs by not more than 1 or not more than 2 nucleotides from SEQ ID NO:1. 
     
     
         12 . The isolated oligonucleotide agent of  claim 10 , wherein the oligonucleotide agent comprises at least two repeats of SEQ ID NO:1. 
     
     
         13 . The isolated oligonucleotide of  claim 10 , wherein said sequence is chosen from the group of: SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, and SEQ ID NO:6. 
     
     
         14 . The oligonucleotide agent of  claim 10 , wherein the oligonucleotide agent is an iRNA agent. 
     
     
         15 . The oligonucleotide agent of  claim 10 , wherein said agent is a single stranded RNA agent. 
     
     
         16 . The isolated oligonucleotide of  claim 10 , further comprising at least one 2′-fluoromodified nucleotide, wherein the 2′-fluoro-modified nucleotide is not part of a sequence of 4 or more contiguous nucleotides from SEQ ID NO:1. 
     
     
         17 . (canceled) 
     
     
         18 . (canceled) 
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . (canceled) 
     
     
         22 . (canceled) 
     
     
         23 . (canceled) 
     
     
         24 . A pharmaceutical composition comprising the oligonucleotide agent of  claim 10  and a pharmaceutically acceptable carrier. 
     
     
         25 . The pharmaceutical composition of  claim 24 , wherein the pharmaceutical composition, is a vaccine. 
     
     
         26 . The method of  claim 7 , further comprising providing the oligonucleotide agent in such manner that it contains at least 2, or at least 4,2′-O-methyl modified nucleotides. 
     
     
         27 . The method of  claim 26 , wherein at least one, or at least two, of the 2′-O-methyl-modified nucleotides is part of a sequence of 4 or more contiguous nucleotides from SEQ ID NO:1.