Micro-RNA mediated modulation of colony stimulating factors
View Patent ↗The present invention relates to the modulation of immunoregulatory proteins, including cytokines, such as colony stimulatory factors (CSF) via the use of microRNA-155 modulators.
1. A method of inhibiting the expression of one or more colony stimulatory factors (CSF) in a mammalian cell, said method comprising administering an inhibitor of microRNA-155 to the mammalian cell in an amount effective to inhibit the expression of said CSF; wherein said inhibitor of microRNA-155comprises an oligomer of between 6 and 30 nucleotides in length, and wherein said oligomer comprises a contiguous nucleotide sequence which is fully complementary to at least six contiguous nucleotides present in the sequence of microRNA-155.
2. The method according to claim 1 , wherein the mammalian cell is selected from the group consisting of monocytes/macrophages, granulocytes, neutrophils, eosinophils, pluripotent haemopoitic stem cell, colony forming units (CFU), and white blood cell precursor cells.
3. The method according to claim 1 , wherein said mammalian cell is over-expressing CSF.
4. The method according to claim 1 , wherein said method is performed in vitro.
5. The method according to claim 1 , wherein said method is performed in vivo.
6. The method according to claim 1 , wherein said oligomer comprises a contiguous nucleotide sequence which is either identical to or is fully complementary to the sequence of the seed region of microRNA-155.
7. The method according to claim 1 , wherein said oligomer consists of a contiguous nucleotide sequence which is either identical to or is fully complementary to the sequence of the seed region of microRNA-155.
8. The method according to claim 1 , wherein the contiguous nucleotide sequence of the oligomer is fully complementary to the sequence of a region of microRNA-155.
9. The method according to claim 1 , wherein the contiguous nucleotide sequence of the oligomer comprises between 7 and 23 nucleotides, which are fully complementary to the sequence of the corresponding region of microRNA-155.
10. The method according to claim 9 , wherein the contiguous nucleotide sequence of the oligomer comprises between 7 and 23 nucleotides which are fully complementary to a sequence found in SEQ ID NO: 2.
11. The method according to claim 9 , wherein the contiguous nucleotide sequence of the oligomer consists of between 7 and 23 nucleotides which are fully complementary to a sequence found in SEQ ID NO: 2.
12. The method according to claim 10 , wherein the contiguous nucleotide sequence of the oligomer comprises between 7 and 16 nucleotides which are fully complementary to a sequence found in SEQ ID NO: 2.
13. The method according to claim 10 , wherein the contiguous nucleotide sequence of the oligomer consists of between 7 and 16 nucleotides which are fully complementary to a sequence found in SEQ ID NO: 2.
14. The method according to claim 10 , wherein the contiguous nucleotide sequence of the oligomer consists of between 8 and 11 nucleotides which are fully complementary to a sequence found in SEQ ID NO: 2.
15. The method according to claim 1 , wherein the oligomer comprises one or more LNA units.
16. The method according to claim 1 , wherein the contiguous nucleotide sequence of the oligomer is any one of SEQ ID NO's: 5 to 25.