Methods of using anti-MIR126 compounds
Provided herein are, inter alia, methods of treating red blood cell disorders and cancer using anti-miR126 compounds. The methods include administering phosphorothioated CpG oligodeoxynucleotides conjugated to an anti-miR126 nucleic acid sequence to treat red blood cell disorders. Other methods provided herein include administering phosphorothioated CpG oligodeoxynucleotides conjugated to an anti-miR126 nucleic acid sequence and a tyrosine kinase inhibitor to treat cancer.
1. A method of treating anemia in a subject in need thereof, said method comprising administering to said subject an effective amount of an anti-microRNA126 (miR126) compound.
2. The method of claim 1 , wherein said anti-miR126 compound comprises:
(i) a phosphorothioated CpG oligodeoxynucleotide (CpG-ODN) conjugated to an anti-miR126 nucleic acid sequence;
(ii) a CpG-ODN conjugated to a miRNA126 mimic nucleic acid sequence; or
(iii) an unconjugated anti-miR126 nucleic acid sequence, wherein said unconjugated anti-miR126 nucleic acid sequence comprises one or more phosphorothioate linkages and one or more chemically modified nucleotides.
3. The method of claim 1 , wherein the compound is administered to the subject by intravenous, parenteral, subcutaneous, intramuscular, transdermal, intraperitoneal, intranasal, aerosol, oral, or topical administration.
4. The method of claim 1 , wherein said treatment is dose-dependent of said compound or composition.
5. The method of claim 1 , wherein about 0.001 mg/kg to about 100 mg/kg of said compound are administered to said subject.
6. A method of forming a red blood cell, said method comprising:
(i) contacting a hematopoietic stem cell (HSC) with an anti-microRNA126 (miR126) compound, thereby forming a contacted HSC; and
(ii) allowing said contacted HSC to divide, thereby forming a red blood cell.
7. The method of claim 6 , wherein said contacting occurs in a subject.
8. The method of claim 6 , wherein said contacting occurs in vitro.
9. The method of claim 6 , wherein said anti-miR126 compound comprises:
(a) a phosphorothioated CpG oligodeoxynucleotide (CpG-ODN) conjugated to an anti-miR 126 nucleic acid sequence;
(b) a CpG-ODN conjugated to a miRNA126 mimic nucleic acid sequence; or
(c) an unconjugated anti-miR126 nucleic acid sequence, wherein said unconjugated anti-miR 126 nucleic acid sequence comprises one or more phosphorothioate linkages and one or more chemically modified nucleotides.
10. A method of treating cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a tyrosine kinase inhibitor and a therapeutically effective amount of an anti-microRNA126 (miR126) compound.
11. The method of claim 10 , wherein said subject is a subject undergoing cancer treatment.
12. The method of claim 10 , wherein the tyrosine kinase inhibitor is dasatinib, bevacizumab, vatalanib, vemurafenib, vandetanib, cabozantinib, poatinib, axitinib, ruxolitinib, regorafenib, crizotinib, bosutinib, lapatinib, lenvatinib, mubritinib, nilotinib, panitumumab or pazopanib.
13. The method of claim 10 , wherein said anti-microRNA126 (miR126) compound is an anti-miR126 nucleic acid.
14. The method of claim 13 , wherein said anti-miR126 nucleic acid comprises the sequence of SEQ ID NO:6.