Materials and methods for reducing inflammation by inhibition of the atrial natriuretic peptide receptor

• US 20070265204A1
• Filed: 04/30/2007
• Published: 11/15/2007
• Est. Priority Date: 02/17/2004
• Status: Active Grant

• Current Assignee: University of South Florida (State University System of Florida)
• Original Assignee: University of South Florida (State University System of Florida)
• Inventors: Wang, Xiaoqin, Xu, Weidong, Mohapatra, Shyam, Kong, Xiaoyuan
• Granted Patent: US 8,071,560 B2
• Time in Patent Office: Days
• US Class Current: 514/44.R
• CPC Class Codes: C12N 15/1138 against receptors or cell surface proteins
• CPC Class Codes: C12N 2310/14 interfering N.A.

Abstract

This invention pertains to inhibitors of atrial natriuretic peptide receptor A (NPRA) function, such as small interfering RNA (siRNA), useful for reducing the inflammation associated with many human diseases, such as asthma, respiratory syncytial virus (RSV) infection, and cancers (such as melanoma, lung cancer, and/or ovarian cancer) by interfering with NPRA gene expression or otherwise reducing NPRA function within a subject; and methods for treating a subject suffering from, or at risk of developing, an inflammatory disease, respiratory allergy (such as allergic rhinitis and asthma), viral infection, and/or cancer by administering such NPRA inhibitors to the subject.

Claims

1. An isolated polynucleotide targeted to a nucleic acid sequence within a natriuretic peptide receptor A (NPRA) gene or NPRA transcript, wherein said polynucleotide inhibits expression of said NPRA gene or transcript.

2. The polynucleotide of claim 1, wherein the NPRA is human NPRA.

3. The polynucleotide of claim 1, wherein the target nucleic acid sequence is at least a portion of the human NPRA gene or transcript.

4. The polynucleotide of claim 1, wherein the target nucleic acid sequence is located in a region selected from the group consisting of the 5′

untranslated region (UTR), transcription start site, translation start site, and 3′

UTR.

5. The polynucleotide of claim 1, wherein the polynucleotide is a small interfering RNA (siRNA).

6. The polynucleotide of claim 1, wherein the polynucleotide is an antisense molecule.

7. The polynucleotide of claim 1, wherein the polynucleotide is a ribozyme.

8. The polynucleotide of claim 1, wherein the polynucleotide comprises SEQ ID NO:

1, or SEQ ID NO;

2, or SEQ ID NO;

3.

9. The polynucleotide of claim 1, wherein the NPRA gene or NPRA transcript is at least a portion of the mammal gene or transcript.

10. A composition comprising the polynucleotide of claim 1;

and a pharmaceutically acceptable carrier.

11. A vector comprising the polynucleotide of claim 1;

and an operably linked promoter.

12. A method for reducing the function of the atrial natriuretic peptide receptor A (NPRA) in a subject, comprising administering an NPRA inhibitor to the subject, wherein the NPRA inhibitor is administered in an effective amount to reduce NPRA function.

13. The method of claim 12, wherein the subject is suffering from an inflammatory disease, respiratory allergy, viral infection, and/or cancer.

14. The method of claim 12, wherein the subject is not suffering from an inflammatory disease, respiratory allergy, viral infection, and/or cancer.

15. The method of claim 12, wherein the subject is human.

16. The method of claim 12, wherein the subject is a non-human mammal.

17. The method of claim 12, wherein the NPRA inhibitor is delivered to cells within the subject selected from the group consisting of respiratory epithelial cells, dendritic cells, and monocytes.

18. The method of claim 12, wherein the NPRA inhibitor is administered to the subject intranasally.

19. The method of claim 12, wherein the NPRA inhibitor is administered intranasally as drops or as an aerosol, or orally or transdermally.

20. The method of claim 12, wherein step of administering comprises administering a combination of NPRA inhibitors to the subject.

21. The method of claim 12, wherein the NPRA inhibitor is a polynucleotide targeted to a nucleic acid sequence within the NPRA gene or transcript, wherein the polynucleotide reduces expression of the NPRA gene or transcript.

22. The method of claim 21, wherein the polynucleotide is an siRNA and wherein the siRNA reduces expression of NPRA within the subject.

23. The method of claim 12, wherein the NPRA inhibitor is an oxindole.

24. The method of claim 23, wherein the NPRA inhibitor is isatin.

25. The method of claim 12, wherein the subject is suffering from respiratory virus infection, melanoma, lung cancer, or ovarian cancer.