miR-126 REGULATED GENES AND PATHWAYS AS TARGETS FOR THERAPEUTIC INTERVENTION

• US 20090131354A1
• Filed: 05/22/2008
• Published: 05/21/2009
• Est. Priority Date: 05/22/2007
• Status: Abandoned Application

• Current Assignee: Mirna Therapeutics, Inc. (Synlogic, Inc.)
• Original Assignee: Mirna Therapeutics, Inc. (Synlogic, Inc.)
• Inventors: Johnson, Charles D., Brown, David, Byrom, Mike W., Bader, Andreas G., Patrawala, Lubna
• Application Number:
  US12/125,675
• Publication Number:
  US 20090131354A1
• Time in Patent Office: Days
• US Class Current: 514/44.R
• CPC Class Codes: A61K 31/7105 Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/106 Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
• CPC Class Codes: C12Q 2600/178 miRNA, siRNA or ncRNA

Abstract

The present invention concerns methods and compositions for identifying genes or genetic pathways modulated by miR-126, using miR-126 to modulate a gene or gene pathway, using this profile in assessing the condition of a patient and/or treating the patient with an appropriate miRNA.

Claims

1. A method of modulating gene expression in a cell comprising administering to the cell an amount of an isolated nucleic acid comprising a miR-126 nucleic acid sequence in an amount sufficient to modulate the expression of one or more genes identified in Table 1, 3, 4, or 5.

2. The method of claim 1, wherein the cell is in a subject having, suspected of having, or at risk of developing a metabolic, an immunologic, an infectious, a cardiovascular, a digestive, an endocrine, an ocular, a genitourinary, a blood, a musculoskeletal, a nervous system, a congenital, a respiratory, a skin, or a cancerous disease or condition.

4. The method of claim 2, wherein the cancerous condition is anaplastic large cell lymphoma, B-cell lymphoma, chronic lymphoblastic leukemia, multiple myeloma, testicular tumor, astrocytoma, acute myeloid leukemia, breast carcinoma, Burkitt'"'"'s lymphoma, bladder carcinoma, cervical carcinoma, colorectal carcinoma, endometrial carcinoma, Ewing'"'"'s sarcoma, glioma, glioblastoma, gastric carcinoma, gastrinoma, hepatoblastoma, hepatocellular carcinoma, Hodgkin lymphoma, leukemia, lung carcinoma, melanoma, mantle cell lymphoma, meningioma, myeloid leukemia, mesothelioma, neurofibroma, non-Hodgkin lymphoma, non-small cell lung carcinoma, ovarian carcinoma, oesophageal carcinoma, oropharyngeal carcinoma, osteosarcoma, pancreatic carcinoma, papillary carcinoma, prostate carcinoma, pheochromocytoma, renal cell carcinoma, rhabdomyosarcoma, squamous cell carcinoma of the head and neck, schwannoma, sporadic papillary renal carcinoma, thyroid carcinoma, or small cell lung cancer wherein the modulation of one or more gene is sufficient for a therapeutic response.

5. The method of claim 4, wherein the cancerous condition is lung carcinoma.

6. The method of claim 5, wherein lung carcinoma is non-small cell lung carcinoma.

8. The method of claim 4, wherein the cancerous condition is prostate carcinoma.

10. The method of claim 8, wherein prostate carcinoma is androgen independent.

11. The method of claim 1, wherein the expression of a gene is down-regulated.

12. The method of claim 1, wherein the expression of a gene is up-regulated.

17. The method of claim 1, wherein the isolated miR-126 nucleic acid is a recombinant nucleic acid.

18. The method of claim 17, wherein the recombinant nucleic acid is RNA or DNA.

20. The method of claim 18, wherein the recombinant nucleic acid comprises a miR-126 expression cassette.

23. The method of claim 1, wherein the miR-126 nucleic acid is a synthetic nucleic acid.

24. The method of claim 23, wherein the nucleic acid is administered at a dose of 0.01 mg/kg of body weight to 10 mg/kg of body weight.

27. The method of claim 1, wherein the nucleic acid is administered enterally or parenterally.

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

31. The method of claim 30, wherein the pharmaceutical formulation is a lipid composition or a nanoparticle composition.

33. The method of claim 30, wherein the pharmaceutical formulation consists of biocompatible and/or biodegradable molecules.

3. (canceled)

7. (canceled)

9. (canceled)

13-16. -16. (canceled)

19. (canceled)

21. (canceled)

22. (canceled)

25. (canceled)

26. (canceled)

28. (canceled)

29. (canceled)

32. (canceled)

34-49. -49. (canceled)

50. A method of treating a patient diagnosed with or suspected of having or suspected of developing a pathological condition or disease related to a gene modulated by a miRNA comprising the steps of:

(a) administering to the patient an amount of an isolated nucleic acid comprising a miR-126 nucleic acid sequence in an amount sufficient to modulate a cellular pathway or a physiologic pathway; and

(b) administering a second therapy, wherein the modulation of the cellular pathway or physiologic pathway sensitizes the patient to the second therapy.

51. (canceled)

52. A method of selecting a miRNA to be administered to a subject with, suspected of having, or having a propensity for developing a pathological condition or disease comprising:

(a) determining an expression profile of one or more genes selected from Table 1, 3, 4, or 5;

(b) assessing the sensitivity of the subject to miRNA therapy based on the expression profile; and

(c) selecting one or more miRNA based on the assessed sensitivity.

53-57. -57. (canceled)