Use of spiegelmers to inhibit an intracellular target molecule
The present invention relates to the use of a L-nucleic acid as intracellularly active agent.
1. A method of inhibiting an intracellular target molecule comprising, contacting a cell with an L-nucleic acid, wherein said L-nucleic acid binds to an intracellular target molecule selected from the group consisting of HMGA1, HMGA1a, HMGA1b and HMGA2, and wherein overexpression of said intracellular target molecule correlates with pathology associated with a disease.
2. The method of claim 1 , wherein said L-nucleic acid comprises a spiegelmer.
3. The method of claim 1 , wherein said L-nucleic acid acts as an intracellular agent.
4. The method of claim 1 , wherein said contacting comprises administrating a pharmaceutically active amount of said L-nucleic acid to a subject in need thereof.
5. The method of claim 3 , wherein said target molecule is associated with a disease or infectious agent.
6. The method of claim 1 , wherein said pathology is associated with a tumor, a virus or arteriosclerosis.
7. The method of claim 1 , further comprising a delivery vehicle.
8. The method of claim 7 , wherein said delivery vehicle comprises a conjugate.
9. The method of claim 7 , wherein said delivery vehicle is a liposome, a nanoparticle, a microparticle, a cyclodextrin, a dendrimer or a vesicle.
10. The method of claim 8 , wherein said conjugate comprises a fusogenic peptide, a signal peptide or a nucleic acid.
11. The method of claim 8 , wherein said conjugate enters a cell by receptor mediated endocytosis.
12. The method of claim 10 , wherein said nucleic acid comprises a spiegelmer.
13. The method of claim 8 , wherein the conjugate is lipophilic.
14. The method of claim 4 , wherein said L-nucleic acid enters said cell by electroporation, iontophoresis, pressure, ultrasound or sound waves.
15. The method of claim 7 , wherein said delivery vehicle comprises polyethyleneimine (PEI).
16. The method of claim 15 , wherein said PEI is branched.
17. The method of claim 15 , wherein said PEI is about 25 kDa.
18. The method of claim 15 , wherein said PEI forms a micelle or micelle-like structure.
19. The method of claim 2 , wherein said spiegelmer comprises a modification.
20. The method of claim 19 , wherein said modification comprises polyethyleneglycol (PEG).
21. The method of claim 20 , wherein said PEG has a molecular weight of about 1,000 to about 10,000 Da.
22. The method of claim 21 , wherein said PEG has a molecular weight of about 1,500 to about 2,500 Da.
23. The method of claim 22 , wherein said PEG is about 2,000 Da.
24. The method of claim 19 , wherein said modification is at a terminus of said spiegelmer.
25. The method of claim 15 , wherein nitrogen of said PEI and phosphate of said nucleic acid are in a ratio of about 1 to about 20.
26. The method of claim 25 , wherein said ratio is about 1.5 to about 10.
27. The method of claim 26 , wherein said ratio is about 2 to about 5.
28. The method of claim 27 , wherein said ratio is about 2 to about 3.