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 composition comprising: 
 an immunostimulatory nucleic acid in association with a targeting means, wherein the nucleic acid comprises a 5′ CG 3′.    
     
     
         20 . The composition of  claim 19 , wherein the immunostimulatory nucleic acid comprises the sequence 5′-Purine, Purine, C, G, Pyrimidine, Pyrimidine-3′.  
     
     
         21 . The composition of  claim 19 , wherein the immunostimulatory nucleic acid comprises an immunostimulatory motif at least 6 base pairs long.  
     
     
         22 . The composition of  claim 20 , wherein at least one Pyrimidine is uracil.  
     
     
         23 . The composition of  claim 19 , wherein the immunostimulatory nucleic acid comprises the sequence 5′-TCG-3′.  
     
     
         24 . The composition of  claim 20 , wherein the immunostimulatory nucleic acid comprises a sequence selected from the group consisting of AACGTT, AGCGTT, GACGTT, GACGTC, AACGCT, and AGCGCT.  
     
     
         25 . The composition of  claim 20 , wherein the immunostimulatory nucleic acid comprises a sequence selected from the group consisting of AACGTT, AGCGTT, and GACGTT.  
     
     
         26 . The composition of  claim 19 , wherein the immunostimulatory nucleic acid further comprises a phosphate backbone modification.  
     
     
         27 . The composition of  claim 26 , wherein the phosphate backbone modification is phosphorothioate or phosphorodithioate.  
     
     
         28 . The composition of  claim 19 , wherein the immunostimulatory nucleic acid further comprises at least one methylated nucleotide.  
     
     
         29 . The composition of  claim 19 , wherein the association is selected from the group consisting of an ionic bond and a covalent bond.  
     
     
         30 . The composition of  claim 19 , wherein the targeting means is a molecule that binds to a target cell.  
     
     
         31 . The composition of  claim 30 , wherein the target cell is selected from the group consisting of a B-cell, and a natural killer cell.  
     
     
         32 . The composition of  claim 19 , wherein the targeting means is selected from the group consisting of a sterol, a lipid, and a target cell specific binding agent.  
     
     
         33 . The composition of  claim 32 , wherein the lipid is selected from the group consisting of a cationic lipid, a virosome, and a liposome.  
     
     
         34 . The composition of  claim 32 , wherein the target cell specific binding agent is a ligand recognized by a target cell specific receptor.  
     
     
         35 . The composition of  claim 19 , wherein the immunostimulatory nucleic acid is associated with a pharmaceutically acceptable carrier.  
     
     
         36 . The composition of  claim 19 , wherein the composition comprises an adjuvant.  
     
     
         37 . The composition of  claim 19 , wherein the immunostimulatory nucleic acid is an oligonucleotide.  
     
     
         38 . The composition of  claim 19 , wherein the immunostimulatory nucleic acid comprises a ribonucleotide.  
     
     
         39 . The composition of  claim 19 , wherein the immunostimulatory nucleic acid comprises a deoxyribonucleotide.  
     
     
         40 . The composition of  claim 19 , wherein the immunostimulatory nucleic acid is from 2 to 100 nucleotides in length.  
     
     
         41 . The composition of  claim 19 , wherein the immunostimulatory nucleic acid is from 8 to 40 nucleotides in length.  
     
     
         42 . The composition of  claim 19 , wherein the immunostimulatory nucleic acid is single stranded.  
     
     
         43 . The composition of  claim 19 , wherein the immunostimulatory nucleic acid comprises a palindromic sequence.  
     
     
         44 . The composition of  claim 19 , wherein the composition comprises a vaccine for treating a virus infection.  
     
     
         45 . The composition of  claim 19 , wherein the composition comprises a vaccine for treating a tumor.  
     
     
         46 . The composition of  claim 19 , wherein the composition comprises a vaccine for treating cancer.  
     
     
         47 . The composition of  claim 19 , wherein the composition comprises a vaccine for treating allergy.  
     
     
         48 . The composition of  claim 19 , wherein the composition comprises a virus antigen.  
     
     
         49 . The composition of  claim 19 , wherein the composition comprises a tumor antigen.  
     
     
         50 . The composition of  claim 19 , wherein the composition comprises an allergen.  
     
     
         51 . The composition of  claim 50 , wherein the allergen is selected from the group consisting of pollen, insect venom, animal dander, dust, fungal spores, and drugs.  
     
     
         52 . The composition of  claim 48 , wherein the wherein the virus is selected from the group consisting of a human immunodeficiency virus, a hepatitis virus, a herpes simplex virus, a  rotavirus , a polio virus, a measles virus, and a papilloma virus.  
     
     
         53 . The composition of  claim 19 , wherein the immunostimulatory nucleic acid comprises a palindromic or non-palindromic double or single-stranded oligonucleotide.  
     
     
         54 . The composition of  claim 19 , further comprising a linear DNA sequence.  
     
     
         55 . The composition of  claim 19 , further comprising a circular DNA sequence.  
     
     
         56 . The composition of  claim 19 , further comprising an RNA nucleotide sequence.  
     
     
         57 . The composition of  claim 56 , wherein the RNA nucleotide sequence comprises a double-stranded nucleic acid sequence.  
     
     
         58 . The composition of  claim 19 , wherein the immunostimulatory nucleic acid comprises at least one modified oligonucleotide.  
     
     
         59 . The composition of  claim 54 , wherein the immunostimulatory nucleic acid is contained within the linear DNA sequence, and further wherein the immunostimulatory nucleic acid comprises a 5′-Purine, Purine, C, G, Pyrimidine, Pyrimidine-3′ nucleotide sequence.  
     
     
         60 . The composition of  claim 55 , wherein the immunostimulatory nucleic acid is contained within the circular DNA nucleotide sequence, and further wherein the immunostimulatory nucleic acid comprises a 5′-Purine, Purine, C, G, Pyrimidine, Pyrimidine-3′ nucleotide sequence.  
     
     
         61 . The composition of  claim 56 , wherein the immunostimulatory nucleic acid is contained within the RNA nucleotide sequence, and further wherein the immunostimulatory nucleic acid comprises a 5′-Purine, Purine, C, G, Pyrimidine, Pyrimidine-3′ nucleotide sequence.  
     
     
         62 . The composition of  claim 20 , wherein the 5′-Purine, Purine, C, G, Pyrimidine, Pyrimidine-3′ nucleotide sequence further comprises a modified nucleotide.  
     
     
         63 . A method of stimulating an immune response comprising the administration of a composition comprising an immunostimulatory nucleic acid in association with a targeting means to a subject to stimulate an immune response.  
     
     
         64 . The method of  claim 63 , wherein the route of administration is a transdermal route.  
     
     
         65 . The method of  claim 63 , wherein the immunostimulatory nucleic acid comprises a DNA or RNA nucleotide sequence.  
     
     
         66 . The method of  claim 65 , wherein the immunostimulatory nucleic acid comprises a CG containing oligonucleotide.  
     
     
         67 . The method of  claim 66 , wherein the CG containing nucleotide sequence is the nucleotide sequence 5′-Purine, Purine, C, G, Pyrimidine, Pyrimidine-3′.  
     
     
         68 . The method of  claim 66 , wherein the CG containing nucleotide sequence is a palindromic or non-palindromic double-stranded or single-stranded oligonucleotide nucleotide sequence.  
     
     
         69 . The method of  claim 66 , wherein the immunostimulatory nucleic acid has a nucleotide sequence selected from the group consisting of AACGTT, AGCGTT, GACGTT, GACGTC, AACGCT, and AGCGCT.  
     
     
         70 . The method of  claim 66 , wherein the immunostimulatory nucleic acid has a nucleotide sequence selected from the group consisting of AACGTT, AGCGTT, and GACGTT.  
     
     
         71 . The method of  claim 63 , wherein the stimulated immune response comprises the induction of a Th1 response.  
     
     
         72 . The method of  claim 63 , wherein the association is selected from the group consisting of an ionic bond and a covalent bond.  
     
     
         73 . The method of  claim 63 , wherein the targeting means is a molecule that binds to a target cell.  
     
     
         74 . The method of  claim 73 , wherein the target cell is selected from the group consisting of a B-cell, and a natural killer cell.  
     
     
         75 . The method of  claim 63 , wherein the targeting means is selected from the group consisting of a sterol, a lipid, and a target cell specific binding agent.  
     
     
         76 . The method of  claim 75 , wherein the lipid is selected from the group consisting of a cationic lipid, a virosome, and a liposome.  
     
     
         77 . The method of  claim 75 , wherein the target cell specific binding agent is a ligand recognized by a target cell specific receptor.  
     
     
         78 . The method of  claim 63 , wherein the immune response is a lymphocyte response.