Immunostimulatory nucleic acid molecules

Abstract

Nucleic acids containing unmethylated CpG dinucleotides and therapeutic utilities based on their ability to stimulate an immune response and to redirect a Th2 response to a Th1 response in a subject are disclosed. Methods for treating atopic diseases, including atopic dermatitis, are disclosed.

1 .- 18 . (canceled)  
     
     
         19 . A method for preventing and/or treating a disorder involving inflammation comprising administering to a subject suffering from such a disorder an effective amount of a nucleic acid comprising a non-methylated CpG motif.  
     
     
         20 . The method of  claim 19  wherein the inflammatory changes are caused by allergens such as pollen, insect venom, fungal spores or drugs.  
     
     
         21 . The method of  claim 19  wherein the inflammatory changes are atopic eczema.  
     
     
         22 . The method of  claim 19  wherein the nucleic acid comprising a non-methylated CpG motif comprises at least one non-methylated central CG dinucleotide flanked at the 5′ end by two purine-containing nucleotides and on the 3′ end by two pyrimidine-containing nucleotides.  
     
     
         23 . The method of  claim 19  wherein the non-methylated CpG motif is 5′-TCC ATG ACG TTC CTG ACG TT-3′ (SEQ ID NO:10) or 5′-GACGTT-3′.  
     
     
         24 . The method of  claim 19  wherein the nucleic acid comprising a non-methylated CpG motif is 2 to 100 nucleotides in length or 8 to 40 nucleotides in length.  
     
     
         25 . The method of  claim 19  wherein the nucleic acid comprising a non-methylated CpG motif is modified.  
     
     
         26 . The method of  claim 25  wherein the modified nucleic acid comprising a non-methylated CpG motif is modified by replacement of phosphodiester bridges with methylphosphonates, phosphoramidates, phosphorothioates or 2′-O-methyl nucleic acids.  
     
     
         27 . The method of  claim 19  wherein the nucleic acid comprising a non-methylated CpG motif is in a liposome.  
     
     
         28 . A pharmaceutical composition for preventing and/or treating a disorder involving inflammation comprising a nucleic acid comprising a non-methylated CpG motif selected from the group consisting of:  
       
         
           
                 
                 
               
                     
                 
                   5′-TCC ATG ACG TTC CTG ACG TT-3′ (SEQ ID NO:10) 
                     
                 
                   or 
                 
                     
                 
                   5′-GACGTT-3′. 
                 
                     
                 
             
                
                
                
                
                
                
               
            
           
         
       
     
     
         29 . The composition of  claim 28  wherein the nucleic acid comprising a non-methylated CpG motif is 2 to 100 nucleotides in length or 8 to 40 nucleotides in length.  
     
     
         30 . The composition of  claim 28  wherein the nucleic acid comprising a non-methylated CpG motif is modified.  
     
     
         31 . The composition of  claim 30  wherein the modified nucleic acid comprising a non-methylated CpG motif is modified by replacement of phosphodiester bridges with methylphosphonates, phosphoramidates, phosphorothioates or 2′-O-methyl nucleic acids.  
     
     
         32 . The composition of  claim 28  wherein the nucleic acid comprising a non-methylated CpG motif is in a liposome.  
     
     
         33 . A process for producing a pharmaceutical composition for preventing and/or treating a disorder involving inflammation comprising mixing at least one nucleic acid comprising a non-methylated CpG motif with at least one and pharmacologically acceptable carrier.  
     
     
         34 . The process of  claim 33  wherein the non-methylated CpG motif is 5′-TCC ATG ACG TTC CTG ACG TT-3′ (SEQ ID NO:10) or 5′-GACGTT-3′.  
     
     
         35 . The process of claim of  claim 33  wherein the at least one nucleic acid comprising a non-methylated CpG motif is modified.  
     
     
         36 . The process of claim of  claim 33  wherein the at least one nucleic acid comprising a non-methylated CpG motif is in a liposome.