NUCLEIC ACID LIGANDS TO LL37

• US 20120121533A1
• Filed: 11/14/2011
• Published: 05/17/2012
• Est. Priority Date: 11/12/2010
• Status: Active Grant

• Current Assignee: BioTex Incorporated
• Original Assignee: BioTex Incorporated
• Inventors: Jackson, George W.
• Granted Patent: US 9,044,495 B2
• Time in Patent Office: Days
• US Class Current: 424/78.36
• CPC Class Codes: A61K 31/713 Double-stranded nucleic acids or oligonucleotides
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: C12N 15/115 Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith ; Nucleic acids binding to non-nucleic acids, e.g. aptamers
• CPC Class Codes: C12N 2310/16 Aptamers
• CPC Class Codes: C12N 2310/334 Modified C
• CPC Class Codes: C12N 2310/335 Modified T or U

Abstract

The present invention is directed to nucleic acid ligands to LL37, methods for producing said nucleic acid ligands, and methods for utilizing said nucleic acid ligands. In one exemplary embodiment, for example, this invention relates to nucleic acid ligands exhibiting high specific binding affinity to LL37 peptides, precursors and/or portions thereof. Further, the nucleic acid ligands may bind competitively with native ligands of LL37 and may also inhibit and/or interfere with LL37 function, such as by binding to LL37.

Claims

1. A composition comprising:

at least one nucleic acid ligand having a specific binding affinity to human LL37, said at least one nucleic acid ligand comprising at least one higher-order-bond modified nucleobase;

wherein said specific binding affinity substantially inhibits the function of said human LL37.

2. The composition of claim 1, wherein said at least one higher-order-bond modified nucleobase comprises an alkene- or alkyne-modified nucleobase.

3. The composition of claim 2, wherein said alkene- or alkyne-modified nucleobase is selected from the group consisting of Amino-allyl deoxyUTP, 5-Propynyl-2′

-deoxycytidine-5′

-Triphosphate, and C8-alkyne-dCTP.

4. The composition of claim 1, wherein said at least one nucleic acid ligand comprises an aptamer substantially homologous to Sequence ID SEQ7.

5. The composition of claim 1, further comprising a solvent, wherein said at least one nucleic acid ligand is substantially dissolved in said solvent.

6. The composition of claim 5, wherein said solvent comprises a permeability enhancing solvent.

7. The composition of claim 1, wherein said at least one nucleic acid ligand comprises a multimeric aptamer comprising at least two aptamers.

8. The composition of claim 7, wherein said multimeric aptamer comprises a chimeric aptamer.

9. The composition of claim 7, wherein said at least two aptamers are linked by a polymeric linkage.

10. The composition of claim 9, wherein said polymeric linkage comprises an oligonucleotide linkage.

11. A method for treatment of a human comprising:

applying a composition to a human tissue, said composition comprising at least one nucleic acid ligand having a specific binding affinity to human LL37, said at least one nucleic acid ligand comprising at least one high-order-bond modified nucleobase;

wherein said at least one high-order-bond modified nucleobase increases transport of said composition into or across said human tissue.

12. The method of claim 11, wherein said at least one nucleic acid ligand binds to and substantially inhibits said human LL37.

13. The method of claim 11, wherein said increased transport comprises increased solubility of said composition in lipid-rich or proteinaceous tissue.

14. The method of claim 11, wherein said at least one high-order-bond modified nucleobase comprises an alkene- or alkyne-modified nucleobase.

15. The method of claim 14, wherein said alkene- or alkyne-modified nucleobase is selected from the group consisting of Amino-allyl deoxyUTP, 5-Propynyl-2′

-deoxycytidine-5′

-Triphosphate, and C8-alkyne-dCTP.

16. The method of claim 11, further comprising applying a solvent to said human tissue.

17. The method of claim 11, wherein said human tissue comprises skin.

18. A composition comprising:

at least one nucleic acid ligand substantially homologous to Sequence ID SEQ7.

19. The composition of claim 18, wherein said at least one nucleic acid ligand comprises at least one alkene-alkyne-modified nucleobase.

20. The composition of claim 19, wherein said alkene- or alkyne-modified nucleobase is selected from the group consisting of Amino-allyl deoxyUTP, 5-Propynyl-2′

-deoxycytidine-5′

-Triphosphate, and C8-alkyne-dCTP.