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 .- 101 . (canceled)
102 . A method for treating liver cancer comprising administering to a subject in need thereof a compound comprising a modified oligonucleotide consisting of 15 to 30 linked nucleosides, wherein the modified oligonucleotide has a nucleobase sequence comprising at least 15 contiguous nucleobases of the DNA sequence complementary to nucleobases 8-29 of SEQ ID NO:32.
103 . The method of claim 102 wherein the liver cancer is hepatocellular carcinoma.
104 . The method of claim 102 wherein the subject is a human.
105 . The method of claim 102 wherein the compound consists of a modified oligonucleotide.
106 . The method of claim 102 wherein the modified oligonucleotide has a nucleobase sequence comprising at least 16, 17, 18, 19, 20, 21, 22, or 23 contiguous nucleobases of the DNA sequence complementary to nucleobases 8-29 of SEQ ID NO:32.
107 . The method of claim 102 wherein the modified oligonucleotide has a nucleobase sequence consisting of the DNA sequence complementary to nucleobases 8-29 of SEQ ID NO:32.
108 . The method of claim 102 wherein at least one internucleoside linkage is a modified internucleoside linkage.
109 . The method of claim 102 wherein the modified internucleoside linkage is a phosphorothioate internucleoside linkage.
110 . The method of claim 102 wherein at least one internucleoside linkage is a modified internucleoside linkage.
111 . The method of claim 102 wherein the modified internucleoside linkage is a phosphorothioate internucleoside linkage.
112 . The method of claim 102 wherein at least one nucleoside comprises a modified sugar.
113 . The method of claim 112 wherein each modified sugar is independently selected from a 2′-fluoro or a 2′-O-methyl sugar moiety.
114 . The method of claim 102 wherein each of a plurality of nucleosides comprises a modified sugar.
115 . The method of claim 112 wherein each modified sugar is independently selected from a 2′-fluoro or a 2′-O-methyl sugar moiety.
116 . The method of claim 102 wherein each nucleoside comprises a modified sugar.
117 . The method of claim 112 wherein each modified sugar is independently selected from a 2′-fluoro or a 2′-O-methyl sugar moiety.
118 . The method of claim 102 wherein at least one nucleoside comprises a modified nucleobase.
119 . The method of claim 118 wherein the modified nucleobase is a 5-methylcytosine.
120 . The method of claim 102 wherein the administering comprises intravenous administration, subcutaneous administration, or intratumoral administration.
121 . The method of claim 102 comprising administering at least one additional therapy, wherein the at least one additional therapy is a chemotherapeutic agent.
122 . The method of claim 121 wherein the chemotherapeutic agent is selected from 5-fluorouracil, gemcitabine, doxorubicine, mitomycin C, etoposide, carboplatin, epirubicin, irinotecan, and oxalilatin.
123 . The method of claim 102 wherein the administering results in reduction of tumor size or tumor number.
124 . The method of claim 102 wherein the administering prevents an increase in tumor size or tumor number.
125 . The method of claim 102 wherein the administering prevents or slows metastatic progression.
126 . The method of claim 102 wherein the administering extends overall survival time or progression-free survival time of the subject.