Immunostimulatory nucleic acid molecules
View Patent ↗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. An immunostimulatory nucleic acid composition comprising
a synthetic nucleic acid comprising an unmethylated CpG dinucleotide,
wherein the nucleic acid contains a diol at either or both termini, wherein the diol is a tetraethyleneglycol or hexaethyleneglycol.
2. An immunostimulatory nucleic acid composition comprising
a synthetic nucleic acid comprising an unmethylated CpG dinucleotide,
wherein the nucleic acid comprises a diol.
3. An immunostimulatory nucleic acid composition comprising
a synthetic nucleic acid comprising an unmethylated CpG dinucleotide,
wherein the nucleic acid comprises a diol at either terminus.
4. An immunostimulatory nucleic acid composition comprising
a synthetic nucleic acid comprising an unmethylated CpG dinucleotide,
wherein the nucleic acid comprises a diol at both termini.
5. The immunostimulatory nucleic acid composition of claim 2 , wherein the diol is tetraethyleneglycol or hexaethyleneglycol.
6. The immunostimulatory nucleic acid composition of any one of claims 1 - 5 , wherein the immunostimulatory nucleic acid composition has the ability to stimulate interferon-gamma or interferon-alpha secretion by spleen cells or human peripheral blood mononuclear cells.
7. The immunostimulatory nucleic acid composition of any one of claims 1 - 5 ,
wherein the synthetic nucleic acid comprises a motif represented by the formula 5′X 1 X 2 CGX 3 X 4 3′, wherein C is unmethylated, and X 1 , X 2 , X 3 and X 4 are nucleotides.
8. The immunostimulatory nucleic acid composition of any one of claims 1 - 5 , wherein the nucleic acid comprises a 5′ TC at its 5′ end.
9. The immunostimulatory nucleic acid composition of any one of claims 1 - 5 , wherein the nucleic acid comprises a 5′ TCG 3′.
10. The immunostimulatory nucleic acid composition of any one of claims 1 - 5 , wherein the nucleic acid comprises a 5′ TCGT 3′.
11. The immunostimulatory nucleic acid composition of any one of claims 1 - 5 , wherein the nucleic acid comprises a phosphodiester backbone.
12. The immunostimulatory nucleic acid composition of any one of claims 1 - 5 , wherein the nucleic acid comprises a modified backbone.
13. The immunostimulatory nucleic acid composition of claim 12 , wherein the nucleic acid is phosphorothioate or phosphorodithioate modified nucleic acid.
14. The immunostimulatory nucleic acid composition of any one of claims 1 - 5 , further comprising a pharmaceutically acceptable carrier.
15. The immunostimulatory nucleic acid composition of any one of claims 1 - 5 , further comprising an antigen.
16. The immunostimulatory nucleic acid composition of claim 1 , further comprising a cationic lipid.
17. The immunostimulatory nucleic acid composition of any one of claims 1 - 5 , wherein the nucleic acid is an oligonucleotide.
18. The immunostimulatory nucleic acid composition of claim 1 , wherein the nucleic acid is less than 100 nucleotides long.
19. The immunostimulatory nucleic acid composition of claim 1 , wherein the nucleic acid is 2-100 nucleotides long.
20. The immunostimulatory nucleic acid composition of claim 1 , wherein the nucleic acid is 6-100 nucleotides long.
21. The immunostimulatory nucleic acid composition of claim 1 , wherein the nucleic acid is 8-40 nucleotides long.
22. The immunostimulatory nucleic acid composition of claim 6 wherein the synthetic nucleic acid comprises a motif represented by the formula 5′X 1 X 2 CGX 3 X 4 3′, wherein C is unmethylated, and X 1 , X 2 , X 3 and X 4 are nucleotides.
23. The immunostimulatory nucleic acid composition of claim 1 , wherein the immunostimulatory nucleic acid comprises an alkyl phosphonate, an aryl phosphonate or alkylphosphotriester.
24. The immunostimulatory nucleic acid composition of claim 2 , wherein the immunostimulatory nucleic acid comprises an alkyl phosphonate, an aryl phosphonate or alkylphosphotriester.
25. The immunostimulatory nucleic acid composition of claim 3 , wherein the immunostimulatory nucleic acid comprises an alkyl phosphonate, an aryl phosphonate or alkylphosphotriester.
26. The immunostimulatory nucleic acid composition of claim 4 , wherein the immunostimulatory nucleic acid comprises an alkyl phosphonate an aryl phosphonate or alkylphosphotriester.
27. The immunostimulatory nucleic acid composition of claim 5 , wherein the immunostimulatory nucleic acid comprises an alkyl phosphonate, an aryl phosphonate or alkylphosphotriester.