Compositions and methods for inhibiting expression of factor VII gene

1. An isolated double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of a Factor VII gene, the dsRNA comprising a sense strand and an antisense strand comprising a region of complementarity which is complementary to at least 15 contiguous nucleotides of SEQ ID NO: 58, the region of complementarity less than 30 nucleotides and each strand 15-30 nucleotides in length.

2. The dsRNA of claim 1 , wherein the dsRNA can reduce liver Factor VII mRNA levels in rats by at least 25% silencing with a single administration of a dose 98N12-5 formulated Factor VII-targeting siRNA.

3. The dsRNA of claim 1 , wherein said dsRNA comprises at least one modified nucleotide.

4. The dsRNA of claim 3 , wherein said modified nucleotide is chosen from the group consisting of: a 2′-O-methyl modified nucleotide, a nucleotide comprising a 5′-phosphorothioate group, and a terminal nucleotide linked to a cholesteryl derivative or dodecanoic acid bisdecylamide group.

5. The dsRNA of claim 3 , wherein said modified nucleotide is chosen from the group consisting of: a 2′-deoxy-2′-fluoro modified nucleotide, a 2′-deoxy-modified nucleotide, a locked nucleotide, an abasic nucleotide, 2′-amino-modified nucleotide, 2′-alkyl-modified nucleotide, morpholino nucleotide, a phosphoramidate, and a non-natural base comprising nucleotide.

6. The dsRNA of claim 1 comprising a phosphorothioate or a 2′-modified nucleotide.

7. The dsRNA of claim 1 , wherein the region of complementarity is 19-21 nucleotides in length.

8. A cell comprising the dsRNA of claim 1 .

9. A pharmaceutical composition, comprising the dsRNA of claim 1 and a pharmaceutically acceptable carrier.

10. A method for inhibiting the expression of a Factor VII gene in a cell, the method comprising:

(a) introducing into the cell the double-stranded ribonucleic acid (dsRNA) of claim 1 ; and

(b) maintaining the cell produced in step (a) for a time sufficient to obtain degradation of the mRNA transcript of the Factor VII gene, thereby inhibiting expression of the Factor VII gene in the cell.

11. A method of treating, preventing or managing a viral hemorrhagic fever comprising administering to a patient in need of such treatment, prevention or management a therapeutically or prophylactically effective amount of the dsRNA of claim 1 .

12. A vector comprising a regulatory sequence operably linked to a nucleotide sequence that encodes at least one strand of the dsRNA of claim 1 .

13. A cell comprising the vector of claim 12 .

14. The dsRNA of claim 1 , wherein said sense strand comprises the nucleotide sequence of SEQ ID NO: 57.

15. The dsRNA of claim 1 , wherein said antisense strand comprises the nucleotide sequence of SEQ ID NO: 58.

16. The dsRNA of claim 1 , wherein said sense strand consists of the nucleotide sequence of SEQ ID NO: 57.

17. The dsRNA of claim 1 , wherein said antisense strand consists of the nucleotide sequence of SEQ ID NO: 58.

18. The dsRNA of claim 1 , wherein said sense strand consists of SEQ ID NO: 57 and said antisense strand consists of SEQ ID NO: 58.

19. The dsRNA of claim 1 , wherein said sense strand consists of SEQ ID NO: 9 and the antisense strand consists of SEQ ID NO: 10, wherein each strand is modified as follows to include a 2′-O-methyl ribonucleotide as indicated by a lower case letter “c” or “u” and a phosphorothioate as indicated by a lower case letter “s”:

SEQ ID NO: 9 is ccuucGAGGGccGGAAcuGdTsdT and

SEQ ID NO: 10 is cAGuuCCGGCCCUCGAAGGdTsdT.