Compositions and methods for modulating angiogenesis
The invention generally features compositions and methods that are useful for modulating angiogenesis.
1. A method of reducing angiogenesis in a subject in need thereof, the method comprising contacting a cell with an effective amount of an antisense nucleic acid molecule complementary to at least a portion of a microRNA nucleic acid molecule of the mir-17-92 cluster,
wherein the antisense nucleic acid molecule comprises a nucleobase sequence having at least 95% identity to a sequence selected from the group consisting of:
(SEQ ID NO: 1)
miR-17-5p:
ACUACCUGCACuGUAAGCACUUUG;
(SEQ ID NO: 2)
mir-18a:
UAUGUGCACUAGAUGCACCUUA;
(SEQ ID NO: 3)
mir-19a:
UCAGUUUUGCAUAGAUUUGCACA;
(SEQ ID NO: 4)
mir-19b:
UCAGUUUUGCAUGGAUUUGCACA;
(SEQ ID NO: 5)
mir-20a:
CUACCUGCACUAUAAGCACUUUA;
and
(SEQ ID NO: 6)
mir-92-1:
CAGGCCGGGACAAGUGCAAUA.
thereby reducing angiogenesis.
2. The method of claim 1 , wherein the antisense nucleic acid molecule decreases the expression of the microRNA in the cell.
3. The method of claim 1 , wherein the cell is present in a tissue or organ.
4. The method of claim 1 , wherein the cell is a neoplastic cell.
5. The method of claim 1 , wherein the cell is an ocular cell.
6. The method of claim 1 , wherein microRNA is mir-19.
7. The method of claim 1 , wherein the microRNA is mir-18.
8. The method of claim 1 , wherein the antisense nucleic acid molecule is an siRNA.
9. A method for increasing the expression of a thrombospondin type 1 repeat (TSR) protein in a cell, the method comprising contacting the cell with an effective amount of an antisense nucleic acid molecule complementary to at least a portion of a microRNA nucleic acid molecule of the mir-17-92 cluster,
wherein the antisense nucleic acid molecule comprises a nucleobase sequence having at least 95% identity to a sequence selected from the group consisting of:
miR-17-5p:
(SEQ ID NO: 1)
ACUACCUGCACuGUAAGCACUUUG;
mir-18a:
(SEQ ID NO: 2)
UAUCUGCACUAGAUGCACCUUA;
mir-19a:
(SEQ ID NO: 3)
UCAGUUUUGCAUAGAUUUGCACA;
mir-19b:
(SEQ ID NO: 4)
UCAGUUUUGCAUGGAUUUGCACA;
mir-20a:
(SEQ ID NO: 5)
CUACCUGCACUAUAAGCACUUUA;
and
mir-92-1:
(SEQ ID NO: 6)
CAGGCCGGGACAAGUGCAAUA,
thereby increasing the expression of a TSR protein.
10. The method of claim 9 , wherein the method increases expression of thrombospondin 1 (Tsp 1) or connective tissue growth factor (CTGF) relative to a control.
11. A method of treating an ocular disease characterized by increased angiogenesis in a subject in need thereof, the method comprising administering to the subject an effective amount of an antisense nucleic acid molecule complementary to at least a portion of a microRNA nucleic acid molecule of the mir-17-92 cluster, wherein the antisense nucleic acid molecule comprises a nucleobase sequence having at least 95% identity to a sequence selected from the group consisting of:
miR-17-5p:
(SEQ ID NO: 1)
ACUACCUGCACuGUAAGCACUUUG;
mir-18a:
(SEQ ID NO: 2)
UAUCUGCACUAGAUGCACCUUA;
mir-19a:
(SEQ ID NO: 3)
UCAGUUUUGCAUAGAUUUGCACA;
mir-19b:
(SEQ ID NO: 4)
UCAGUUUUGCAUGGAUUUGCACA;
mir-20a:
(SEQ ID NO: 5)
CUACCUGCACUAUAAGCACUUUA;
and
mir-92-1:
(SEQ ID NO: 6)
CAGGCCGGGACAAGUGCAAUA,
thereby treating an ocular disease.