MCP-1 binding nucleic acids
The present invention is related to a nucleic acid, preferably binding to MCP-1, selected from the group consisting of Type 1A nucleic acids, type 1B nucleic acids, Type 2 nucleic acids, Type 3 nucleic acids, Type 4 nucleic acids and nucleic acids comprising SEQ ID NOs:87-115.
1. An L-nucleic acid that binds a chemokine, wherein the nucleic acid comprises in direction a first stretch Box B1A, a second stretch Box B2, and a third stretch Box B1B, wherein the first stretch Box B1A comprises a nucleotide sequence selected from the group consisting of ACGCA, CGCA and GCA, the second stretch Box B2 comprises CSUCCCUCACCGGUGCAAGUGAAGCCGYGGCUC (SEQ ID NO:287), and the third stretch Box B1B comprises a nucleotide sequence selected from the group consisting of UGCG and UGC.
2. The nucleic acid according to claim 1 , wherein the second stretch Box B2 comprises CGUCCCUCACCGGUGCAAGUGAAGCCGUGGCUC (SEQ ID NO:288).
3. The nucleic acid according to claim 1 , wherein
a) the first stretch Box B1A comprises ACGCA, and
the third stretch Box B1B comprises UGCGU;
b) the first stretch Box B1A comprises CGCA, and
the third stretch Box B1B comprises UGCG; or
c) the first stretch Box B1A comprises GCA, and
the third stretch Box B1B comprises UGC or UGCG.
4. The nucleic acid according to claim 1 , wherein the first stretch Box B1A comprises GCA.
5. The nucleic acid according to claim 1 , wherein the third stretch Box B1B comprises UGCG.
6. The nucleic acid according to claim 1 , wherein the chemokine is selected from the group consisting of eotaxin, MCP-1, MCP-2 and MCP-3.
7. The nucleic acid according to claim 1 , wherein the chemokine is human MCP-1.
8. The nucleic acid according to claim 1 , comprising a modification.
9. The nucleic acid according to claim 8 , wherein the modification comprises hydroxyethyl starch (HES) moiety or a polyethylene glycol (PEG) moiety.
10. The nucleic acid according to claim 8 , wherein the modification comprises a straight or a branched PEG.
11. The nucleic acid according to claim 10 , wherein said straight or branched PEG has a molecular weight from about 20 kD to about 120 kD.
12. The nucleic acid according to claim 9 , wherein said HES moiety has a molecular weight from about 10 kD to about 130 kD.
13. The nucleic acid according to claim 1 , wherein the first stretch Box B1A and the third stretch Box B1B optionally hybridize with each other to form a double-stranded structure.
14. A pharmaceutical composition comprising a nucleic acid according to claim 1 and a pharmaceutically acceptable excipient, carrier, pharmaceutically active agent or combination thereof.
15. A method for treating a disease associated with a chemokine comprising exposing a subject suspected of having said disease with the nucleic acid of claim 1 .
16. The method of claim 15 , wherein said chemokine comprises human MCP-1.
17. A method for detecting a chemokine comprising exposing a sample suspected of comprising said chemokine with the nucleic acid of claim 1 and determining presence of complexes of said nucleic acid and said chemokine, wherein presence of complexes correlates with presence of chemokine in said sample.
18. The method of claim 17 , wherein said chemokine comprises eotaxin, MCP-1, MCP-2 or MCP-3.
19. A method for identifying a chemokine antagonist or agonist comprising the steps:
providing a candidate chemokine antagonist and/or a candidate chemokine agonist,
providing the nucleic acid according to claim 1 ,
providing a test system which provides a signal in the presence of complexes of the chemokine and said nucleic acid, Wherein a chemokine antagonist and/or chemokine agonist interferes with formation of said complexes, and
determining whether an antagonist and/or an agonist identified in the test system is an antagonist and/or agonist of said chemokine.
20. The method of claim 19 , wherein said chemokine is selected from the group consisting of eotaxin, MCP-1, MCP-2 and MCP-3.
21. The method of claim 19 , wherein said test system comprises a solid phase, and said chemokine is immobilized on said solid phase.