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. A nucleic acid delivery complex comprising
an immunostimulatory oligonucleotide six nucleotides long having a sequence 5′ X 1 X 2 CGX 3 X 4 3′, wherein the C is unmethylated and X 1 , X 2 , X 3 , and X 4 are nucleotides;
wherein the immunostimulatory oligonucleotide comprises at least a partial phosphorothioate modified backbone; and,
wherein the immunostimulatory oligonucleotide is associated with a targeting means chosen from a sterol, a lipid, and a target cell specific binding ligand.
2. The nucleic acid delivery complex of claim 1 , wherein the immunostimulatory oligonucleotide is ionically bound to the targeting means.
3. The nucleic acid delivery complex of claim 1 , wherein the immunostimulatory oligonucleotide is covalently bound to the targeting means.
4. The nucleic acid delivery complex of claim 1 , wherein the immunostimulatory oligonucleotide is encapsulated within the targeting means.
5. The nucleic acid delivery complex of claim 1 , wherein the targeting means is a liposome.
6. The nucleic acid delivery complex of claim 1 , wherein the targeting means is a cationic lipid.
7. A method of inducing a Th1 response and suppressing a Th2 response in a subject, the method comprising administering to a subject a nucleic acid delivery complex in an effective amount to induce a Th1 response and suppress a Th2 response in the subject, wherein the nucleic acid delivery complex comprises an immunostimulatory oligonucleotide six nucleotides long having a sequence 5′ X 1 X 2 CGX 3 X 4 3′, wherein the C is unmethylated and X 1 , X 2 , X 3 and X 4 are nucleotides;
wherein the immunostimulatory oligonucleotide comprises at least a partial phosphorothioate modified backbone; and,
wherein the immunostimulatory oligonucleotide is associated with a targeting means chosen from a sterol, a lipid, and a target cell specific binding ligand.
8. The method of claim 7 , wherein the subject has a disease mediated by a Th2 type immune response.
9. The method of claim 8 , wherein the disease mediated by a Th2 type immune response is chosen from allergy and asthma.
10. The method of claim 7 , further comprising administering a vaccine to the subject.
11. The method of claim 7 , wherein the subject has a cancer.
12. The method of claim 7 , wherein the subject has an infection.
13. The method of claim 12 , wherein the infection is a viral infection.
14. The method of claim 12 , wherein the infection is a fungal infection.
15. The method of claim 14 , wherein the fungal infection is an infection with Toxoplasma gondii.
16. The method of claim 12 , wherein the infection is a bacterial infection.
17. The method of claim 16 , wherein the bacterial infection is an infection with a species of Mycobacteria.
18. The method of claim 12 , wherein the infection is a parasitic infection.
19. The method of claim 18 , wherein the parasitic infection is an infection with Plasmodium falciparum.