NGF aptamer and application thereof

1. An aptamer binding to NGF and forming a secondary structure represented by the formula (I):

wherein N is one nucleotide selected from the group consisting of A, G, C, U and T,

N11-N13, N21-N23, N32-N38 and N42-N48 are the same or different and each is a bond or 1 or 2 nucleotides selected from the group consisting of A, G, C, U and T,

N14, N24, N31, N41, N39 and N49 are the same or different and each is one nucleotide selected from the group consisting of A, G, C, U and T,

N14 and N24, N31 and N41, and N39 and N49 each form a Watson-Crick base pair,

N11-N12-N13-N14 and N21-N22-N23-N24 are nucleotide sequences forming a stem structure of stem 1 in combination,

N31-N32-N33-N34-N35-N36-N37-N38-N39 and N41-N42-N43-N44-N45-N46-N47-N48-N49 are nucleotide sequences forming a stem structure of stem 2 in combination, and

the final base pair of stem 1 is U-a.

2. The aptamer according to claim 1 , wherein N11-N13, N21-N23, N32-N38 and N42-N48 are the same or different and each is one nucleotide selected from the group consisting of A, G, C, U and T.

3. The aptamer according to claim 1 , wherein N14 is U, N24 is A, N31 is G, N41 is C, N39 is G, and N49 is C.

4. The aptamer according to claim 1 , wherein not less than 4 Watson-Crick base pairs are formed between N32-N33-N34-N35-N36-N37-N38 and N42-N43-N44-N45-N46-N47-N48.

5. The aptamer according to claim 1 , which is the following (a) or (b):

(a) a nucleic acid consisting of a nucleotide sequence selected from SEQ ID NO: 3, SEQ ID NOs: 9-13, SEQ ID NOs: 22-117 and SEQ ID NOs: 152-168 (wherein uracil may be thymine);

(b) a nucleic acid binding to NGF and consisting of the nucleotide sequence of the above-mentioned (a), wherein 1 to several nucleotides are substituted, deleted, inserted or added.

6. The aptamer according to claim 1 , which has a base length of not more than 50.

7. The aptamer according to claim 1 , wherein at least one nucleotide is modified.

8. The aptamer according to claim 7 , which is modified with inverted dT or polyethylene glycol.

9. The aptamer according to claim 8 , wherein the inverted dT or polyethylene glycol is bound to the 5′ end or 3′ end of the aptamer.

10. The aptamer according to claim 7 , wherein the hydroxyl groups at the 2′-position of a ribose of respective pyrimidine nucleotides are the same or different and unreplaced or replaced by an atom or group selected from the group consisting of a hydrogen atom, a fluorine atom and a methoxy group.

11. The aptamer according to claim 7 , wherein the hydroxyl groups at the 2′-position of a ribose of respective purine nucleotides are the same or different and unreplaced or replaced by an atom or group selected from the group consisting of a hydrogen atom, a fluorine atom and a methoxy group.

12. The aptamer according to claim 1 , which inhibits neurite outgrowth activity and/or cell proliferation activity of NGF.

13. A pharmaceutical composition comprising the aptamer according to claim 1 and a pharmaceutically acceptable carrier.

14. A composition comprising the aptamer according to claim 1 suitable for use as an anti-pain agent.

15. A composition comprising the aptamer according to claim 1 suitable for use as an anti-inflammatory agent.

16. A method of treating a disease accompanying a pain or inflammation, comprising administering the aptamer according to claim 1 to a subject in need thereof.

17. The method of claim 16 , wherein the disease accompanies pain selected from the group consisting of nociceptive pain, inflammatory pain, neuropathic pain, carcinomatous pain and fibromyalgia pain.

18. The method of claim 16 , wherein the disease accompanies inflammation selected from the group consisting of systemic lupus erythematosus, multiple sclerosis, psoriasis, osteoarthritis, rheumatoid arthritis, interstitial cystitis and asthma.

19. A method of treating a disease accompanying a pain or inflammation, comprising administering the aptamer according to claim 5 to a subject in need thereof.

20. The method of claim 19 , wherein the disease accompanies pain selected from the group consisting of nociceptive pain, inflammatory pain, neuropathic pain, carcinomatous pain and fibromyalgia pain.

21. The method of claim 19 , wherein the disease accompanies inflammation selected from the group consisting of systemic lupus erythematosus, multiple sclerosis, psoriasis, osteoarthritis, rheumatoid arthritis, interstitial cystitis and asthma.