miR-124 Regulated Genes and Pathways as Targets for Therapeutic Intervention

• US 20090192111A1
• Filed: 12/01/2008
• Published: 07/30/2009
• Est. Priority Date: 12/01/2007
• Status: Active Grant

• Current Assignee: Mirna Therapeutics, Inc. (Synlogic, Inc.)
• Original Assignee: Asuragen, Inc.
• Inventors: Wiggins, Jason F., Byrom, Mike, Brown, David, Kelnar, Kevin, Bader, Andreas G., Patrawala, Lubna
• Granted Patent: US 8,071,562 B2
• Time in Patent Office: Days
• US Class Current: 514/44.00R
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C12N 15/113 Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing when used in plants C12N15/8218
• CPC Class Codes: C12N 15/1135 against oncogenes or tumor suppressor genes
• CPC Class Codes: C12N 2310/141 MicroRNAs, miRNAs
• CPC Class Codes: C12N 2330/10 naturally occurring

Abstract

The present invention concerns methods and compositions for identifying genes or genetic pathways modulated by miR-124, using miR-124 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-124 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 condition.

5. The method of claim 2, wherein the cancerous condition is astrocytoma, anaplastic large cell lymphoma, acute lymphoblastic leukemia, acute myeloid leukemia, angiosarcoma, breast carcinoma, B-cell lymphoma, Burkitt'"'"'s lymphoma, bladder carcinoma, cholangiocarcinoma, cervical carcinoma, carcinoma of the head and neck, chronic lymphoblastic leukemia, chronic myeloid leukemia, colorectal carcinoma, endometrial carcinoma, Ewing'"'"'s sarcoma, glioma, glioblastoma, glioblastoma multiforme, gastric carcinoma, hepatoblastoma, hepatocellular carcinoma, Hodgkin lymphoma, Kaposi'"'"'s sarcoma, leukemia, lung carcinoma, lipoma, leiomyosarcoma, liposarcoma, laryngeal squamous cell carcinoma, melanoma, mucosa-associated lymphoid tissue B-cell lymphoma, medulloblastoma, mantle cell lymphoma, myxofibrosarcoma, meningioma, multiple myeloma, neuroblastoma, non-Hodgkin lymphoma, nasopharyngeal carcinoma, non-small cell lung carcinoma, ovarian carcinoma, oesophageal carcinoma, oropharyngeal carcinoma, osteosarcoma, pancreatic carcinoma, papillary carcinoma, prostate carcinoma, retinoblastoma, renal cell carcinoma, rhabdomyosarcoma, squamous cell carcinoma of the head and neck, schwannoma, small cell lung cancer, salivary gland tumor, thyroid carcinoma, testicular tumor, urothelial carcinoma, or Wilm'"'"'s tumor wherein the modulation of one or more gene is sufficient for a therapeutic response.

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

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

8. The method of claim 7, wherein non-small cell lung carcinoma is an adenocarcinoma, squamous cell carcinoma, large cell carcinoma or a bronchioalveolar carcinoma.

9. The method of claim 5, wherein the cancerous condition is prostate carcinoma.

10. The method of claim 9, wherein prostate carcinoma is associated with detectable prostate-specific antigen (PSA).

11. The method of claim 9, wherein prostate carcinoma is androgen independent.

12. The method of claim 5, wherein the cancerous condition is liver carcinoma.

13. The method of claim 12, wherein liver carcinoma is hepatoma, hepatocarcinoma or an hepatic adenocarcinoma.

14. The method of claim 12, wherein liver carcinoma is hepatoblastoma, or a cholangiocarcinoma.

22. The method of claim 1, wherein the isolated miR-124 nucleic acid is a recombinant nucleic acid.

28. The method of claim 1, wherein the miR-124 nucleic acid is a synthetic nucleic acid.

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

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

35. The method of claim 34, wherein the pharmaceutical formulation is a lipid composition or a nanoparticle composition.

37. The method of claim 34, wherein the pharmaceutical formulation consists of biocompatible and biodegradable molecules.

3. (canceled)

4. (canceled)

15-21. -21. (canceled)

23-27. -27. (canceled)

29. (canceled)

30. (canceled)

32. (canceled)

33. (canceled)

36. (canceled)

38-53. -53. (canceled)

54. 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-124 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.

55-59. -59. (canceled)

60. A method of assessing a cell, tissue, or subject comprising assessing expression of miR-124 in combination with assessing expression of one or more gene from Table 1, 3, 4, or 5 in at least one sample.

61. (canceled)