Use of spiegelmers
The present invention relates to the use of a L-nucleic acid as intracellularly active agent.
1. An HMGA-binding nucleic acid comprising a first section, Box A1, and a second section, Box A2, wherein Box A1 and Box A2 are joined to one another by an intermediate portion, and wherein Box A1 and Box A2 each is, independently of one another, GGGCG, GGGUG or GGGAG, and the intermediate portion comprises (a) Z1 comprising six or seven nucleotides or (b) Z2 comprising 12 to 25 nucleotides, and the 5′ end of Box A1 comprises a first portion and the 3′ end of Box A2 comprises a second portion, wherein each of said first and second portions, independently of one another, comprises four to eight nucleotides.
2. The HMGA-binding, nucleic acid of claim 1 selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:6, SEQ :ID NO:7, SEQ ID NO:8, SEQ NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ NO:12, SEQ NO:13, SEQ ID NO:14, SEQ ID NO:15 and SEQ ID NO:16, SEQ ID NO:22 and SEQ ID NO:24.
3. The HMGA-binding nucleic acid of claim 1 , wherein the HMGA is selected from the group consisting of HMGA1, HMGA1a, HMGA1b and HMGA2.
4. A composition comprising the nucleic acid of claim 1 and a delivery vehicle.
5. The composition according to claim 4 , which intracellularly delivers said nucleic acid.
6. The composition according to claim 4 , wherein said delivery vehicle is selected from the group consisting of a conjugate and a physical means.
7. The composition according to claim 4 , wherein said delivery vehicle is selected from the group consisting of a liposome, a nanoparticle, microparticle, a dendrimer and a cyclodextrin.
8. The composition of claim 4 , wherein said delivery vehicle comprises a vesicle comprising a polypeptide, a polyethyleneimine (PEI), an amphipathic molecule or combinations thereof.
9. The composition according to claim 4 , wherein said delivery vehicle comprises a conjugate, wherein said conjugate comprises a fusogenic peptide, a receptor that mediates endocytosis, a signal peptide or a lipophilic molecule.
10. The composition according to claim 4 , wherein said delivery vehicle comprises electroporation, iontophoresis, pressure, ultrasound or shock waves.
11. The composition according to claim 8 , wherein said PEI comprises branches, and said PEI comprises a molecular weight of about 25 kDa.
12. The composition according to claim 8 , wherein said PEI forms a micelle or a micelle-like structure,
13. The composition according to claim 4 , wherein said nucleic acid comprises a spiegelmer.
14. The composition according to claim 13 , wherein said spiegelmer comprises a modification.
15. The composition of claim 14 , wherein said modification comprises polyethylene glycol (PEG).
16. The composition according to claim 15 , wherein said PEG comprises a molecular weight of about 1,000 to 10,000 Da; about 1,500 to 2,500 Da; or about 2.000 Da.
17. The composition according to claim 8 , wherein ratio of nitrogen groups of the PEI to phosphate groups of the nucleic acid is about 1 to 20; about 1.5 to 10; about 2 to 5; or about 2 to 3.
18. A pharmaceutical composition comprising the nucleic acid according to claim 1 , and a pharmaceutically acceptable carrier.
19. A kit for the detection of HMGA, comprising the HMGA-binding nucleic acid according to claim 1 and optional reagents.
20. A complex comprising an HMGA protein and the HMGA-binding nucleic acid according to claim 1 .
21. A method for binding an HMGA comprising:
providing a cell comprising at least one HMGA,
providing the nucleic acid of claim 1 , and
incubating the cell with the nucleic acid.
22. The method according to claim 21 , wherein said nucleic acid comprises a spiegelmer.