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 pharmaceutical composition comprising a synthetic miR-126 molecule.
103 . The pharmaceutical composition of claim 102 , wherein the synthetic miR 126 is non-naturally occurring and markedly different in sequence from naturally occurring miR-126.
104 . The pharmaceutical composition of claim 102 , wherein the synthetic miR-126 is non-naturally occurring and markedly different in chemical structure from naturally occurring miR-126.
105 . The pharmaceutical composition of claim 102 , further comprising a carrier or lipid to increase cellular uptake of the synthetic miR-126 molecule.
106 . The pharmaceutical composition of claim 102 , wherein the pharmaceutical composition is a sterile aqueous solution.
107 . The pharmaceutical composition of claim 102 , wherein the synthetic miR-126 molecule is in a liposomal pharmaceutical delivery system.
108 . The pharmaceutical composition of claim 102 , farther comprising an antibacterial or antifungal agent.
109 . The pharmaceutical composition of claim 102 , wherein the pharmaceutical composition comprises at least about 0.1%, about 2% to about 75%, or about 25% to about 60% by weight of the synthetic miR-126 molecule.
110 . The pharmaceutical composition of claim 102 , wherein the synthetic miR-126 molecule is at least about 95, 96, 97, 98, 99, or 100% pure.
111 . The pharmaceutical composition of claim 102 , wherein the pharmaceutical composition is aliquoted in a vial, test tube, flask, bottle, syringe, or container.
112 . The pharmaceutical composition of claim 102 , wherein the synthetic miR-126 molecule is 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.
113 . The pharmaceutical composition of claim 102 , formulated for administration intravenously or by injection.
114 . The pharmaceutical composition of claim 102 , wherein the synthetic miR-126 comprises a 15-30 nucleobase synthetic oligonucleotide having a sequence that is at least 80% identical to a mature miR-126 sequence.
115 . The pharmaceutical composition of claim 114 , wherein the sequence is not naturally occurring.
116 . The pharmaceutical composition of claim 114 , wherein at least one nucleobase is chemically modified.
117 . The pharmaceutical composition of claim 114 , further comprising a complementary strand that is at least 60% complementary to the synthetic oligonucleotide.
118 . The pharmaceutical composition of claim 117 , wherein the complementary strand is not naturally occurring.
119 . The pharmaceutical composition of claim 117 , wherein the complementary strand comprises a chemical modification that improve uptake of the synthetic oligonucleotide.
120 . The pharmaceutical composition of claim 117 , wherein the complementary strand comprises a chemical modification that enhances activity of the synthetic oligonucleotide.
121 . The pharmaceutical composition of claim 117 , wherein the complementary strand comprises a chemical modification that enhances stability of the synthetic oligonucleotide.
122 . The pharmaceutical composition of claim 117 , wherein the complementary strand comprises a chemical modification that inhibit uptake of the complementary strand.
123 . The pharmaceutical composition of claim 117 , wherein the complementary strand comprises a chemical modification that inhibits activity of the complementary strand.
124 . The pharmaceutical composition of claim 117 , wherein the complementary strand comprises one or more nucleobases that are non-complementary with the synthetic oligonucleotide.