MicroRNA-based methods and assays for osteosarcoma

Patent metadata

Field	Value
Publication number	US-9322016-B2
Application number	US-201214240178-A
Country	US
Kind code	B2
Filing date	Sep 7, 2012
Priority date	Sep 7, 2011
Publication date	Apr 26, 2016
Grant date	Apr 26, 2016

Abstract

Provided are methods and compositions useful in the diagnosis, treatment, and monitoring of osteosarcoma. Antisense to certain microRNA (miRNA) found to be associated with cancer stem cells (CSCs) or tumor-initiating cells (TICs) of osteosarcoma are useful to suppress tumor growth and metastasis, and prolong survival. Antisense oligonucleotides to miR-133a are synergistic in combination with standard chemotherapy such as cisplatin in the treatment of osteosarcoma.

First claim

We claim:

1. A method of treating osteosarcoma, comprising administering to a subject in need thereof an effective amount of an antisense molecule specific for microRNA (miRNA) miR-133a, thereby treating the osteosarcoma.

2. The method of claim 1 , wherein the antisense molecule is stabilized RNA.

3. The method of claim 2 , wherein the stabilized RNA is a locked nucleic acid (LNA) oligonucleotide.

4. The method of claim 1 , wherein the antisense molecule is DNA.

5. The method of claim 1 , wherein the antisense molecule is 20-30 nucleotides long and comprises a nucleotide sequence at least 90 percent identical to 5′-CAGCTGGTTGAAGGGGACCAA-3′ (SEQ ID NO:6).

6. The method of claim 1 , wherein the sequence of the antisense molecule is 5′-CAGCTGGTTGAAGGGGACCAA-3′ (SEQ ID NO:6).

7. The method of claim 1 , wherein the antisense molecule is 20-30 nucleotides long and comprises a nucleotide sequence at least 90 percent identical to 5′-CAGCTGGTTGAAGGGGACCAAA-3′ (SEQ ID NO:12).

8. The method of claim 7 , wherein the sequence of the antisense molecule is 5′-CAGCUGGUUGAAGGGGACCAAA-3′ (SEQ ID NO:9) or 5′-CAGCTGGTTGAAGGGGACCAAA-3′ (SEQ ID NO:12).

9. The method of claim 1 , wherein the antisense molecule is associated with a nucleic acid delivery vehicle.

Assignees

• Ochiya Takahiro
• Fujiwara Tomohiro
• 3 D Matrix Ltd
• Nat Cancer Ct

Inventors

• Ochiya Takahiro
• Fujiwara Tomohiro

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C12N15/113 Primary

  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 title

• C12Q1/6886

  for cancer (immunoassay for cancer G01N33/575) · CPC title

• A61B10/025

  for taking bone, bone marrow or cartilage samples · CPC title

• G01N33/5011

  for testing antineoplastic activity · CPC title