MicroRNA compositions and methods
View Patent ↗Provided herein are compositions comprising oligomeric compounds. In certain embodiments, the oligomeric compounds are useful as miRNA mimics. The oligomeric compounds may mimic the activity of miR-34. Also provided herein are methods for the treatment of cancer.
1. A method of treating liver cancer comprising intravenously administering to a subject having liver cancer a composition comprising an oligomeric compound comprising a first oligonucleotide consisting of 19 to 23 linked nucleosides, wherein the nucleobase sequence of the first oligonucleotide has at least 90% identity with the nucleobase sequence of SEQ ID NO: 1 with 100% identity with nucleobases 2 to 7 of SEQ ID NO: 1, wherein the oligomeric compound comprises a second oligonucleotide hybridized to the first oligonucleotide, wherein the second oligonucleotide consists of 19 to 23 linked nucleosides and wherein the second oligonucleotide is complementary to the first oligonucleotide, and wherein the oligomeric compound is formulated in a liposome.
2. The method of claim 1 wherein the liver cancer is hepatocellular carcinoma.
3. The method of claim 1 wherein the subject is a human.
4. The method of claim 1 comprising administering at least one additional therapy.
5. The method of claim 4 wherein the at least one additional therapy comprises a chemotherapeutic agent.
6. The method of claim 5 wherein the chemotherapeutic agent is selected from 5-fluorouracil, gemcitabine, doxorubicine, mitomycin c, sorafenib, etoposide, carboplatin, epirubicin, irinotecan and oxaliplatin.
7. The method of claim 1 comprising selecting a subject having a p-53 deficient cancer.
8. The method of claim 1 , wherein the liposome comprises at least one lipid selected from phosphatidylcholine (PC), 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC), lecithin, phosphatidylethanolamine (PE), lysolecithin, lysophosphatidylethanolamine, sphingomyelin (SM), cardiolipin, phosphosphatidic acid, 1,2-Distearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-Dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE), 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1,2-Dilauroyl-sn-glycero-3-phosphocholine (DLPC), 1,2-Dimyristoyi-sn-glycero-3-phosphocholine (DMPC), 1,2-Dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-Dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE), 1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), dipalmitoloeoyl-PE, diphytanoyl-PE, DSPE, dielaidoyl-PE, dilinoleoyl-SM, and dilinoleoyl-PE.
9. The method of claim 1 , wherein the complementary oligonucleotide comprises a 5′ terminus cap or a 3′ terminus cap, or a 5′ terminus cap and a 3′ terminus cap.
10. The method of claim 9 , wherein the complementary oligonucleotide comprises a 5′ terminus cap.
11. The method of claim 9 , wherein the cap is selected from a 4′,5′-methylene nucleotide, a 1-(beta-D-erythrofuranosyl) nucleotide, a 4′-thio nucleotide, a carbocyclic nucleotide, a 1,5-anhydrohexitol nucleotide, an L-nucleotide, an alpha-nucleotide, a modified base nucleotide, a phosphorodithioate linkage, a threo-pentofuranosyl nucleotide, an acyclic 3′,4′-seco nucleotide, an acyclic 3,4-dihydroxybutyl nucleotide, an acyclic 3,5-dihydroxypentyl nucleotide, a 3′-3′-inverted nucleotide moiety, a 3′-3′-inverted abasic moiety, a 3′-2′-inverted nucleotide moiety, a 3′-2′-inverted abasic moiety, a 1,4-butanediol phosphate, a 3′-phosphoramidate, a hexylphosphate, an aminohexyl phosphate, a 3′-phosphate, a 3′-phosphorothioate, a phosphorodithioate, a bridging methylphosphonate moiety, and a non-bridging methylphosphonate moiety 5′-amino-alkyl phosphate, a 1,3-diamino-2-propyl phosphate, 3-aminopropyl phosphate, a 6-aminohexyl phosphate, a 1,2-aminododecyl phosphate, a hydroxypropyl phosphate, a 5′-5′-inverted nucleotide moiety, a 5′-5′-inverted abasic moiety, a 5′-phosphoramidate, a 5′-phosphorothioate, a 5′-amino, a bridging and/or non-bridging 5′-phosphoramidate, a phosphorothioate, and a 5′-mercapto moiety.
12. The method of claim 1 , wherein the complementary oligonucleotide is at least 90% complementary to the oligonucleotide.
13. The method of claim 1 , wherein the complementary oligonucleotide is 100% complementary to the oligonucleotide.
14. The method of claim 1 , wherein the central complementary region of the oligomeric compound has 0, 1, or 2 mismatches between the oligonucleotide and the complementary oligonucleotide.
15. The method of claim 1 , wherein the hybridization of the complementary oligonucleotide to the oligonucleotide forms an overhang at each 3′ terminus, wherein the overhang has two nucleosides.