Nucleic acid oligomers and uses therefor
Disclosed are nucleic acid oligomer compounds and to their use in compositions and methods for inhibiting proliferation, survival or viability of cancer cells including prostate, lung, pancreatic, breast, cervical and bone cancer cells.
1. A nucleic acid oligomer of up to 29 nucleobases in length, comprising the nucleobase sequence set forth in SEQ ID NO:1, wherein the nucleobase oligomer comprises a backbone comprising phosphorothioate internucleoside linkages.
2. The nucleic acid oligomer of claim 1 , wherein at least 70% of the internucleoside linkages of the backbone comprise phosphorothioate internucleoside linkages.
3. The nucleic acid oligomer of claim 1 , wherein all internucleoside linkages are phosphorothioate internucleoside linkages.
4. The nucleic acid oligomer of claim 1 , wherein the nucleobase oligomer further comprises 2′-O-alkyl nucleosides.
5. The nucleic acid oligomer of claim 4 , wherein at least 50% of the nucleosides of the oligomer are each a 2′-O-alkyl nucleoside.
6. The nucleic acid oligomer of claim 4 , wherein all nucleosides of the oligomer are each a 2′-O-alkyl nucleoside.
7. The nucleic acid oligomer of claim 4 , wherein the 2′-O-alkyl nucleosides are 2′-O-methyl nucleosides.
8. The nucleic acid oligomer of claim 1 , consisting of the nucleobase sequence set forth in SEQ ID NO:1.
9. The nucleic acid oligomer of claim 1 , comprising mC*mC*mA*mG*mU*mG*mA*mG*mC*mC*mG*mG*mA*mC*mU*mU*mG*mC*mC*mU, wherein m represents a 2′OMe-modified nucleoside, and * represents a phosphorothioate internucleoside linkage.
10. The nucleic acid oligomer of claim 1 , consisting of mC*mC*mA*mG*mU*mG*mA*mG*mC*mC*mG*mG*mA*mC*mU*mU*mG*mC*mC*mU, wherein m represents a 2′OMe-modified nucleoside, and * represents a phosphorothioate internucleoside linkage.
11. A pharmaceutical composition comprising the nucleic acid oligomer of claim 1 and a pharmaceutically acceptable carrier.
12. The pharmaceutical composition of claim 11 , further comprising at least one cancer therapy agent.
13. The pharmaceutical composition of claim 12 , wherein the at least one cancer therapy agent is a radiotherapy agent, a chemotherapy agent, a hormone ablation therapy agent, a pro-apoptosis therapy agent or an immunotherapy agent.
14. The pharmaceutical composition of claim 12 , wherein the at least one cancer therapy agent targets rapidly dividing cells and/or disrupts the cell cycle or cell division.