Use of specific siRNA against protein S for the treatment of hemophilia
The invention provides an siRNA against protein S for use in a method of treatment of hemophilia. Also within the scope of the present invention is a method for treating hemophilia in a patient in need thereof, comprising administering to the patient a molecule comprising a siRNA according to the invention, and a dosage form for the prevention or treatment of hemophilia, comprising a molecule comprising a siRNA according to the invention.
1. A method for treating hemophilia in a subject in need thereof, the method comprising administering to the subject an siRNA against Protein S, said siRNA comprising 17-24 nucleotides and comprising a hybridizing sequence having 100% sequence identity to a corresponding portion of a sequence that is the reverse complement of SEQ ID NO: 001, said siRNA being capable of mediating RNA interference of Protein S when administered to a Protein S-expressing cell.
2. The method of claim 1 , wherein said hybridizing sequence comprises deoxynucleotides, phosphothioate deoxynucleotides, phosphothioate ribonucleotides and/or 2′-O-methyl-modified phosphothioate ribonucleotides.
3. The method of claim 1 , wherein said siRNA is a double-stranded siRNA.
4. The method of claim 1 , wherein said siRNA comprises a hybridizing sequence having 100% sequence identity to a corresponding portion of a sequence that is the reverse complement of SEQ ID NO: 004 or SEQ ID NO: 017.
5. The method of claim 1 , said siRNA comprising a hybridizing sequence having 100% sequence identity to a corresponding portion of a sequence that is the reverse complement of nucleotides 501-600 or 2201-2300 of SEQ ID NO: 001.
6. The method of claim 1 , wherein said siRNA comprises a hybridizing sequence comprising or consisting of SEQ ID NO: 028 (siRNA_10), SEQ ID NO: 029 (siRNA_11), SEQ ID NO: 030 (siRNA_12), SEQ ID NO: 056 (siRNA_38).
7. The method of claim 1 , wherein said siRNA is directed against an intronic sequence of Protein S.
8. The method of claim 1 , wherein the hemophilia is selected from hemophilia A, hemophilia B, and hemophilia C.
9. A method for improving thrombin generation in a subject in need thereof, said method comprising administering an siRNA against Protein S, said siRNA comprising 17-24 nucleotides and comprising a hybridizing sequence having 100% sequence identity to a corresponding portion of a sequence that is the reverse complement of SEQ ID NO: 001, said siRNA being capable of mediating RNA interference of Protein S when administered to a Protein S-expressing cell.
10. The method of claim 9 , wherein said hybridizing sequence comprises deoxynucleotides, phosphothioate deoxynucleotides, phosphothioate ribonucleotides and/or 2′-O-methyl-modified phosphothioate ribonucleotides.
11. The method of claim 9 , wherein said siRNA is a double-stranded siRNA.
12. The method of claim 9 , wherein said siRNA comprises a hybridizing sequence having 100% sequence identity to a corresponding portion of a sequence that is the reverse complement of SEQ ID NO: 004 or SEQ ID NO: 017.
13. The method of claim 9 , said siRNA comprising a hybridizing sequence having 100% sequence identity to a corresponding portion of a sequence that is the reverse complement of nucleotides 501-600 or 2201-2300 of SEQ ID NO: 001.
14. The method of claim 9 , wherein said siRNA comprises a hybridizing sequence comprising or consisting of SEQ ID NO: 028 (siRNA_10), SEQ ID NO: 029 (siRNA_11), SEQ ID NO: 030 (siRNA_12), SEQ ID NO: 049 (siRNA_31), or SEQ ID NO: 056 (siRNA_38).
15. The method of claim 9 , wherein said siRNA is directed against an intronic sequence of Protein S.
16. A method for reducing the expression of Protein S in a cell, the method comprising administering an siRNA said siRNA comprising 17-24 nucleotides and comprising a hybridizing sequence having 100% sequence identity to a corresponding portion of a sequence that is the reverse complement of SEQ ID NO: 001, said siRNA being capable of mediating RNA interference of Protein S when administered to a Protein S-expressing cell.
17. The method of claim 16 , wherein said hybridizing sequence comprises deoxynucleotides, phosphothioate deoxynucleotides, phosphothioate ribonucleotides and/or 2′-O-methyl-modified phosphothioate ribonucleotides.
18. The method of claim 16 , wherein said siRNA is a double-stranded siRNA.
19. The method of claim 16 , wherein said siRNA comprises a hybridizing sequence having 100% sequence identity to a corresponding portion of a sequence that is the reverse complement of SEQ ID NO: 004 or SEQ ID NO: 017.
20. The method of claim 16 , wherein said siRNA comprises a hybridizing sequence having 100% sequence identity to a corresponding portion of a sequence that is the reverse complement of nucleotides 501-600 or 2201-2300 of SEQ ID NO: 001.
21. The method of claim 16 , wherein said siRNA comprises a hybridizing sequence comprising or consisting of SEQ ID NO: 028 (siRNA_10), SEQ ID NO: 029 (siRNA_11), SEQ ID NO: 030 (siRNA_12), SEQ ID NO: 049 (siRNA_31), or SEQ ID NO: 056 (siRNA_38).
22. The method of claim 16 , wherein said siRNA is directed against an intronic sequence of Protein S.