METHODS AND COMPOSITIONS INVOLVING MIRNA AND MIRNA INHIBITOR MOLECULES
The present invention concerns methods and compositions for introducing miRNA activity or function into cells using synthetic nucleic acid molecules. Moreover, the present invention concerns methods and compositions for identifying miRNAs with specific cellular functions that are relevant to therapeutic, diagnostic, and prognostic applications wherein synthetic miRNAs and/or miRNA inhibitors are used in library screening assays.
1 . A method of treating hepatocellular carcinoma in an individual in need thereof, comprising administering to the individual a therapeutically-effective amount of miRNA inhibitor comprising a nucleic acid sequence that is at least 90% complementary to a miR-221 sequence.
2 . The method of claim 1 , wherein the miRNA inhibitor comprises a sequence that is at least 90% complementary to 5-110 nucleotides of SEQ ID NO: 170.
3 . The method of claim 1 , wherein the miRNA inhibitor comprises a sequence that is at least 90% complementary to at least 50 contiguous nucleotides of SEQ ID NO: 170.
4 . The method of claim 1 , wherein the miRNA inhibitor comprises a sequence that is at least 90% complementary to at least 25 contiguous nucleotides of SEQ ID NO: 170.
5 . The method of claim 1 , wherein the miRNA inhibitor comprises a sequence that is at least 90% complementary to at least 23 contiguous nucleotides of SEQ ID NO: 170.
6 . The method of claim 1 , wherein the miRNA inhibitor comprises a sequence that is at least 90% complementary to at least 20 contiguous nucleotides of SEQ ID NO: 170.
7 . The method of claim 1 , wherein the miRNA inhibitor comprises a sequence that is at least 90% complementary to at least 15 contiguous nucleotides of SEQ ID NO: 170.
8 . The method of claim 1 , wherein the miRNA inhibitor comprises a sequence that is at least 90% complementary to at least 10 contiguous nucleotides of SEQ ID NO: 170.
9 . The method of claim 1 , wherein the miRNA inhibitor comprises a sequence that is at least 90% complementary to at least 5 contiguous nucleotides of SEQ ID NO: 170.
10 . The method of claim 1 , wherein the miRNA inhibitor comprises a sequence that is at least 90% complementary to nucleotides 65-87 of SEQ ID NO: 170.
11 . The method of claim 1 , wherein the miRNA inhibitor comprises a sequence that is at least 90% complementary to a mature, naturally-occurring miR-221 sequence.
12 . The method of claim 1 , wherein the miRNA inhibitor further comprises a pendant group conjugated to an end of the nucleic acid sequence.
13 . The method of claim 1 , wherein the miRNA inhibitor is administered subcutaneously or intravenously.