METHODS AND COMPOSITIONS FOR DIAGNOSING AND MODULATING HUMAN PAPILLOMAVIRUS (HPV)

• US 20090258928A1
• Filed: 04/08/2009
• Published: 10/15/2009
• Est. Priority Date: 04/08/2008
• Status: Abandoned Application

• Current Assignee: Asuragen, Inc., Northwestern University
• Original Assignee: Asuragen, Inc., Northwestern University
• Inventors: Laimins, Laimonis, Li, Gu, Beaudenon-Huibregtse, Sylvie, Langfield, Laura, Labourier, Emmanuel
• Application Number:
  US12/420,634
• Publication Number:
  US 20090258928A1
• Time in Patent Office: Days
• US Class Current: 514/44.A
• CPC Class Codes: A61P 31/20 for DNA viruses
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C12N 15/1131 against viruses
• CPC Class Codes: C12N 2310/113 targeting other non-coding nucleic acids, e.g. antagomirs
• CPC Class Codes: C12N 2310/141 MicroRNAs, miRNAs
• CPC Class Codes: C12N 2330/10 naturally occurring
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 1/708 for papilloma
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: C12Q 2600/178 miRNA, siRNA or ncRNA

Abstract

The present invention concerns methods and compositions for treating a patient having, suspected of having, or at risk of obtaining a HPV infection.

Claims

1. A method of modulating Human Papillomavirus (HPV) infection of a cell comprising administering to the cell an isolated

(a) nucleic acid inhibitor of hsa-miR-199a, hsa-miR-199a-AS, hsa-miR-214, hsa-miR-145, hsa-miR-143, hsa-miR-151, hsa-miR-30a_—

5p, hsa-miR-130a, hsa-miR-197, hsa-miR-181b, hsa-miR-130b and/or hsa-miR-203;

or

(b) nucleic acid having a hsa-miR-503, hsa-miR-194, hsa-miR-491, hsa-miR-224, hsa-miR-96, hsa-miR-132, hsa-miR-30e-5p, hsa miR-200a, and/or ambi-miR-7027 activity;

in an amount sufficient to modulate HPV infection.

2. The method of claim 1, wherein a hsa-miR-503 is administered.

3. The method of claim 1, wherein an inhibitor of hsa-miR-199a, hsa-miR-199a-AS, hsa-miR-214, hsa-miR-145, hsa-miR-143, hsa-miR-151, hsa-miR-30a_—

5p is administered.

6. The method of claim 1, wherein the cell is in a subject having, suspected of having, or at risk of developing a HPV infection.

7. The method of claim 6, wherein the HPV infection is associated with a precancerous or cancerous condition.

8. The method of claim 7, wherein the precancerous condition is cervical intraepithelial neoplasia (CIN).

9. The method of claim 1, wherein the cell is a cancer cell.

10. The method of claim 1 wherein the cell is a keratinocyte.

11. The method of claim 1 wherein said HPV infection is reduced.

12. The method of claim 1 wherein said HPV infection is eliminated

13. The method of claim 1, wherein the isolated therapeutic nucleic acid is a recombinant nucleic acid.

19. The method of claim 1, wherein the therapeutic nucleic acid is a synthetic nucleic acid.

22. The method of claim 1, wherein the nucleic acid is comprised in a pharmaceutical formulation.

23. The method of claim 22, wherein the pharmaceutical formulation is a lipid composition, a nanoparticle composition, or a biocompatible and biodegradable composition.

26. The method of claim 1, further comprising administering 2, 3, 4, 5, 6, or more therapeutic nucleic acids.

27. The method claim 26, wherein the miRNAs are comprised in a single composition.

28. The method of claim 1, wherein viability of the cell is reduced, proliferation of the cell is reduced, metastasis of the cell is reduced, or the cell'"'"'s sensitivity to therapy is increased.

4. (canceled)

5. (canceled)

14-18. -18. (canceled)

20. (canceled)

21. (canceled)

24. (canceled)

25. (canceled)

29. (canceled)

30. (canceled)

31. A method of selecting a miRNA to be administered to a subject suspected of having, or having a propensity for developing a HPV infection comprising:

(a) determining an expression profile of one or more miRNA selected from ambi-miR-7027, hsa-miR-30a_—

5p, hsa-miR-30e_—

5p, hsa-miR-96, hsa-miR-130a, hsa-miR-130b, hsa-miR-132, hsa-miR-143, hsa-miR-145, hsa-miR-151, hsa-miR-181b, hsa-miR-194, hsa-miR-197, hsa-miR-199a, hsa-miR-199a-AS, hsa-miR-200a, hsa-miR-203, hsa-miR-214, hsa-miR-224, hsa-miR-491, and/or hsa-miR-503;

(b) assessing the sensitivity of the subject to a therapeutic nucleic acid based on the expression profile; and

(c) selecting one or more therapeutic nucleic acid for administration to the patient based on the assessed sensitivity.

32-34. -34. (canceled)

35. A method of detecting HPV infection in a biological sample comprising evaluating expression levels of hsa-mir-199a, hsa-miR-199a-AS, hsa-miR-214, hsa-miR-145, hsa-miR-143, hsa-miR-151, hsa-miR-503, hsa-miR-30a_—

5p, hsa-miR-200a, or combinations thereof.

36. The method of claim 35, wherein the biological sample is from a mucous membrane, skin, cervix, anus, rectum, penis, vulva, vagina, oropharynx, nasopharynx, trachea, esophagus, or epiglottis.

37-41. -41. (canceled)