Methods of use of bcl-6-derived nucleotides to induce apoptosis
View Patent ↗This invention provides methods of inducing apoptosis in a bcl- 6 -expressing cell and methods of treating a subject with a cancer comprising a bcl- 6 -expressing cell, comprising administration of a composition that reduces the amount of the bcl-6 protein or of an mRNA molecule encoding same, a composition comprising a nucleic acid molecule complementary to or corresponding to a region of the mRNA molecule, or a vector expressing the nucleic acid molecule. In another embodiment, the present invention provides an isolated nucleic acid molecule having a sequence corresponding to or complementary to accessible regions of bcl-6 mRNA, and vectors, cells, compositions, and kits comprising same.
1. A method of inducing apoptosis in a bcl-6-expressing cell, comprising contacting said bcl-6-expressing cell with a composition that reduces an amount of said bcl-6 protein or of a ribonucleic acid molecule encoding said bcl-6 protein, thereby inducing apoptosis in a bcl-6-expressing cell, wherein said composition comprises a nucleic acid molecule complementary to the sequence set forth in SEQ ID NO: 6.
2. The method of claim 1 , wherein said cell is a lymphoma cell.
3. The method of claim 2 , wherein said lymphoma cell is a non-Hodgkin's lymphoma cell.
4. A method of treating a subject with a lymphoma comprising a bcl-6-expressing lymphoma cell, comprising contacting said subject with a composition that reduces an amount of said bcl-6 protein or of a ribonucleic acid molecule encoding said bcl-6 protein, thereby treating said subject with said lymphoma, wherein said composition comprises a nucleic acid molecule complementary to the sequence set forth in SEQ ID NO: 6.
5. The method of claim 4 , wherein said lymphoma is a non-Hodgkin's lymphoma.
6. A method of inducing apoptosis in a bcl-6-expressing cell, comprising contacting said bcl-6-expressing cell with a composition comprising a nucleic acid molecule complementary to the sequence set forth in SEQ ID NO: 6, thereby inducing apoptosis in a bcl-6-expressing cell.
7. The method of claim 6 , wherein said cell is a lymphoma cell.
8. The method of claim 7 , wherein said lymphoma cell is a non-Hodgkin's lymphoma cell.
9. The method of claim 6 , wherein said nucleic acid molecule is an oligo-deoxyribonucleic acid (ODN) molecule.
10. A method of treating a subject with a lymphoma comprising a bcl-6-expressing lymphoma cell, comprising contacting said subject with a composition comprising a nucleic acid molecule complementary to the sequence set forth in SEQ ID NO: 6, thereby treating said subject with said lymphoma.
11. The method of claim 10 , wherein said lymphoma is a non-Hodgkin's lymphoma.
12. The method of claim 10 , wherein said nucleic acid molecule is an oligo-deoxyribonucleic acid (ODN) molecule.
13. A method of inducing apoptosis in a bcl-6-expressing cell, comprising contacting said bcl-6-expressing cell with a composition comprising a nucleic acid molecule corresponding to the sequence set forth in SEQ ID NO: 6, thereby inducing apoptosis in a bcl-6-expressing cell.
14. The method of claim 13 , wherein said cell is a lymphoma cell.
15. The method of claim 14 , wherein said lymphoma cell is a non-Hodgkin's lymphoma cell.
16. The method of claim 13 , wherein said nucleic acid molecule is a short interfering ribonucleic acid (siRNA) molecule.
17. The method of claim 13 , wherein said nucleic acid molecule is a short hairpin RNA (shRNA) molecule.
18. A method of treating a subject with a lymphoma comprising a bcl-6-expressing lymphoma cell, said method comprising contacting said subject with a composition comprising a nucleic acid molecule corresponding to the sequence set forth in SEQ ID NO: 6, thereby treating said subject with said lymphoma.
19. The method of claim 18 , wherein said lymphoma is a non-Hodgkin's lymphoma.
20. The method of claim 18 , wherein said nucleic acid molecule is a short interfering ribonucleic acid (siRNA) molecule.
21. The method of claim 18 , wherein said nucleic acid molecule is a short hairpin RNA (shRNA) molecule.
22. A method of inducing apoptosis in a bcl-6-expressing cell, comprising contacting said bcl-6-expressing cell with a vector expressing a nucleic acid molecule complementary to the sequence set forth in SEQ ID NO: 6, thereby inducing apoptosis in said bcl-6-expressing cell.
23. The method of claim 22 , wherein said cell is a lymphoma cell.
24. The method of claim 23 , wherein said lymphoma cell is a non-Hodgkin's lymphoma cell.
25. The method of claim 22 , wherein said vector is a lentiviral vector.
26. The method of claim 22 , wherein said nucleic acid molecule is an oligo-deoxyribonucleic acid (ODN) molecule.
27. A method of treating a subject with a lymphoma comprising a bcl-6-expressing lymphoma cell, comprising contacting said subject with a vector expressing a nucleic acid molecule complementary to the sequence set forth in SEQ ID NO: 6, thereby treating said subject with said lymphoma.
28. The method of claim 27 , wherein said lymphoma is a non-Hodgkin's lymphoma.
29. The method of claim 27 , wherein said vector is a lentiviral vector.
30. The method of claim 27 , wherein said nucleic acid molecule is an oligo-deoxyribonucleic acid (ODN) molecule.
31. A method of inducing apoptosis in a bcl-6-expressing cell, comprising contacting said bcl-6-expressing cell with a vector expressing a nucleic acid molecule corresponding to the sequence set forth in SEQ ID NO: 6, thereby inducing apoptosis in said bcl-6-expressing cell.
32. The method of claim 31 , wherein said cell is a lymphoma cell.
33. The method of claim 32 , wherein said lymphoma cell is a non-Hodgkin's lymphoma cell.
34. The method of claim 31 , wherein said vector is a lentiviral vector.
35. The method of claim 31 , wherein said nucleic acid molecule is a short interfering ribonucleic acid (siRNA) molecule.
36. The method of claim 31 , wherein said nucleic acid molecule is a short hairpin RNA (shRNA) molecule.
37. A method of treating a subject with a lymphoma comprising a bcl-6-expressing lymphoma cell, comprising contacting said subject with a vector expressing a nucleic acid molecule corresponding to the sequence set forth in SEQ ID NO: 6, thereby treating said subject with said lymphoma.
38. The method of claim 37 , wherein said lymphoma is a non-Hodgkin's lymphoma.
39. The method of claim 37 , wherein said vector is a lentiviral vector.
40. The method of claim 37 , wherein said nucleic acid molecule is a short interfering ribonucleic acid (siRNA) molecule.
41. The method of claim 37 , wherein said nucleic acid molecule is a short hairpin RNA (shRNA) molecule.
42. The method of claim 6 , wherein said contacting reduces the amount of the bcl-6 protein expressed by said bcl-6-expressing cell or of a ribonucleic acid (RNA) molecule encoding said bcl-6 protein.
43. The method of claim 10 , wherein said contacting reduces the amount of the bcl-6 protein expressed by said bcl-6-expressing cell or of a ribonucleic acid (RNA) molecule encoding said bcl-6 protein.
44. The method of claim 13 , wherein said contacting reduces the amount of the bcl-6 protein expressed by said bcl-6-expressing cell or of a ribonucleic acid (RNA) molecule encoding said bcl-6 protein.
45. The method of claim 18 , wherein said contacting reduces the amount of the bcl-6 protein expressed by said bcl-6-expressing cell or of a ribonucleic acid (RNA) molecule encoding said bcl-6 protein.
46. The method of claim 22 , wherein said contacting reduces the amount of the bcl-6 protein expressed by said bcl-6-expressing cell or of a ribonucleic acid (RNA) molecule encoding said bcl-6 protein.
47. The method of claim 27 , wherein said contacting reduces the amount of the bcl-6 protein expressed by said bcl-6-expressing cell or of a ribonucleic acid (RNA) molecule encoding said bcl-6 protein.
48. The method of claim 31 , wherein said contacting reduces the amount of the bcl-6 protein expressed by said bcl-6-expressing cell or of a ribonucleic acid (RNA) molecule encoding said bcl-6 protein.
49. The method of claim 37 , wherein said contacting reduces the amount of the bcl-6 protein expressed by said bcl-6-expressing cell or of a ribonucleic acid (RNA) molecule encoding said bcl-6 protein.