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 synthetic miR-34 molecule.
103 . The synthetic miR-34 molecule of claim 102 , wherein the synthetic miR-34 is non-naturally occurring and markedly different in sequence from naturally occurring miR-34.
104 . The synthetic miR-34 molecule of claim 102 , wherein the synthetic miR-34 is non-naturally occurring and markedly different in chemical structure from naturally occurring miR-34.
105 . The synthetic miR-34 molecule of claim 102 , wherein the synthetic miR-34 comprises a 15-30 nucleobase synthetic oligonucleotide having a sequence that is at least 80% identical to a mature miR-34 sequence.
106 . The synthetic miR-34 molecule of claim 105 , wherein the sequence is not naturally occurring.
107 . The synthetic miR-34 molecule of claim 105 , wherein at least one nucleobase is chemically modified.
108 . The synthetic miR-34 molecule of claim 105 , further comprising a complementary strand that is at least 60% complementary to the synthetic oligonucleotide.
109 . The synthetic miR-34 molecule of claim 108 , wherein the complementary strand is not naturally occurring.
110 . The synthetic miR-34 molecule of claim 108 , wherein the complementary strand comprises a chemical modification that improve uptake of the synthetic oligonucleotide.
111 . The synthetic miR-34 molecule of claim 108 , wherein the complementary strand comprises a chemical modification that enhance activity of the synthetic oligonucleotide.
112 . The synthetic miR-34 molecule of claim 108 , wherein the complementary strand comprises a chemical modification that enhance stability of the synthetic oligonucleotide.
113 . The synthetic miR-34 molecule of claim 108 , wherein the complementary strand comprises a chemical modification that inhibit uptake of the complementary strand.
114 . The synthetic miR-34 molecule of claim 108 , wherein the complementary strand comprises a chemical modification that inhibits activity of the complementary strand.
115 . The synthetic miR-34 molecule of claim 108 , wherein the complementary strand comprise one or more nucleobases that are non-complementary with the synthetic oligonucleotide.
116 . The synthetic miR-34 molecule of claim 108 , in a sterile aqueous solution.
117 . The synthetic miR-34 molecule of claim 116 , in a non-natural liposome.
118 . The synthetic miR-34 molecule of claim 116 , wherein the solution further comprises an antibacterial or antifungal agent.
119 . The synthetic miR-34 molecule of claim 116 , wherein the synthetic miR-34 molecule is at least about 0.1%, about 2% to about 75%, or about 25% to about 60% by weight of the solution.
120 . The synthetic miR-34 molecule of claim 116 , wherein the synthetic miR-34 molecule is at least about 95, 96, 97, 98, 99, or 100% pure.
121 . The synthetic miR-34 molecule of claim 116 , wherein the solution is aliquoted in a vial, test tube, flask, bottle, syringe, or container.
122 . The synthetic miR-34 molecule of claim 116 , in a dose of about 1 μg/kg body weight, about 5 μg/kg body weight, about 10 μg/kg body weight, about 50 μg/kg body weight, about 100 μg/kg body weight, about 200 μg/kg body weight, about 350 μg/kg body weight, about 500 μg/kg body weight, about 5 mg/kg body weight, about 10 mg/kg body weight, about 50 mg/kg body weight, about 100 mg/kg body weight, about 200 mg/kg body weight, about 350 mg/kg body weight, about 500 mg/kg body weight, about 1000 mg/kg body weight, about 5 mg/kg body weight to about 100 mg/kg body weight, or about 5 μg/kg body weight to about 500 mg/kg body weight.
123 . The synthetic miR-34 molecule of claim 116 , wherein the solution is formulated for administration to a subject intravenously or by injection.
124 . A method comprising administering an effective amount of the synthetic miR-34 molecule of claim 102 to a subject in need thereof.
125 . A use of synthetic miR-34 molecule of claim 102 for treating a disease or a condition in a subject.