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 of inhibiting the activity of a microRNA comprising: contacting a cell comprising the microRNA with a compound comprising an oligomeric compound, wherein: the oligomeric compound is at least 90% complementary to a miRNA or a precursor thereof; the oligomeric compound consists of 17 to 25 linked monomeric subunits; at least one monomeric subunit is a modified nucleoside; and the miRNA is selected from miR-21 (nucleotides 8-29 of SEQ ID NO:32) and miR-1 (nucleotides 53-73 of SEQ ID NO:1).
103 . The method of claim 102 , wherein the miRNA is miR-21 (nucleotides 8-29 of SEQ ID NO:32).
104 . The method of claim 102 , wherein the miRNA is miR-1 (nucleotides 53-73 of SEQ ID NO:1).
105 . The method of claim 102 , wherein the oligomeric compound is at least 95% complementary to the miRNA.
106 . The method of claim 102 , wherein the oligomeric compound is 100% complementary to the miRNA.
107 . The method of claim 102 , wherein the oligomeric compound is 100% complementary to at least an 8-nucleobase portion of the miRNA.
108 . The method of claim 102 , wherein the oligomeric compound consists of 21 to 22 linked monomeric subunits.
109 . The method of claim 102 wherein the oligomeric compound consists of an oligonucleotide.
110 . The method of claim 109 wherein the oligonucleotide consists of 21 to 22 linked nucleosides.
111 . The method of claim 102 , wherein the oligomeric compound comprises at least one modified sugar moiety.
112 . The method of claim 111 wherein the modified sugar moiety is 2′-O-methyl.
113 . The method of claim 102 , wherein the oligomeric compound comprises at least one modified internucleoside linkage.
114 . The method of claim 113 , wherein the modified internucleoside linkage is a phosphorothioate linkage.
115 . The method of claim 102 , wherein each monomeric subunit comprises a modified sugar moiety.
116 . The method of claim 102 , wherein the oligonucleotide comprises two or more chemically distinct regions.
117 . The method of claim 116 , wherein each nucleoside of the two or more chemically distinct regions is a 2′-O-methyl nucleoside.
118 . The method of claim 102 , wherein the oligomeric compound comprises at least one modified nucleobase.
119 . The method of claim 102 , wherein the oligomeric compound is attached to a conjugate group.
120 . The method of claim 119 , wherein the conjugate group is cholesterol.
121 . A composition comprising a compound comprising an oligomeric compound, wherein: the oligomeric compound is at least 90% complementary to a miRNA or a precursor thereof; the oligomeric compound consists of 17 to 25 linked monomeric subunits; at least one monomeric subunit is a modified nucleoside; and the miRNA is selected from miR-21 (nucleotides 8-29 of SEQ ID NO:32) and miR-1 (nucleotides 53-73 of SEQ ID NO:1) and a pharmaceutically acceptable diluent or carrier.