Immunostimulatory nucleic acid molecules
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.