Compositions and methods for inhibiting expression of factor V
View Patent ↗The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of Factor V, comprising an antisense strand having a nucleotide sequence which is less that 25 nucleotides in length and which is substantially complementary to at least a part of Factor V. The invention also relates to a pharmaceutical composition comprising the dsRNA together with a pharmaceutically acceptable carrier; methods for treating diseases caused by the expression of Factor V using the pharmaceutical composition; and methods for inhibiting the expression of Factor V in a cell.
1. An isolated double-stranded ribonucleic acid (dsRNA) compound comprising a sense strand and an antisense strand, wherein the nucleotide sequence of the sense strand comprises the nucleotide sequence of SEQ ID NO: 3 and the nucleotide sequence of the antisense strand comprises the nucleotide sequence of SEQ ID NO: 4, respectively.
2. The dsRNA of claim 1 , wherein the sense strand consists of the nucleotide sequence of SEQ ID NO: 3 and the antisense strand consists of the nucleotide sequence of SEQ ID NO: 4, respectively.
3. The dsRNA of claim 1 , wherein the dsRNA comprises at least one modified nucleotide.
4. The dsRNA of claim 3 , wherein said modified nucleotide is chosen from the group 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 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. An isolated cell comprising the dsRNA of claim 1 .
7. The cell of claim 6 , wherein the cell is a mammalian cell.
8. A pharmaceutical composition comprising the dsRNA of claim 1 and a pharmaceutically acceptable carrier.
9. A method for inhibiting the expression of a Factor V gene in a cell, the method comprising:
(a) introducing into the cell the dsRNA of claim 1 ; and
(b) maintaining the cell for a time sufficient to obtain degradation of the mRNA transcript of the Factor V gene, thereby inhibiting the expression of the Factor V gene in the cell.
10. The method of claim 9 , wherein the cell is a mammalian cell.
11. A vector comprising a regulatory sequence operably linked to a nucleotide sequence that encodes at least one strand of the dsRNA of claim 1 .
12. A cell comprising the vector of claim 11 .
13. The cell of claim 12 , wherein the cell is a mammalian cell.
14. The vector of claim 11 , comprising at least one regulatory sequence operably linked to at least one nucleotide sequence that encodes the sense strand and antisense strand of the dsRNA of claim 1 .
15. A cell comprising the vector of claim 14 .
16. The cell of claim 15 , wherein the cell is a mammalian cell.
17. A pharmaceutical composition comprising the dsRNA of claim 2 and a pharmaceutically acceptable carrier.
18. A method for inhibiting the expression of a Factor V gene in a cell, the method comprising:
(a) introducing into the cell the dsRNA of claim 3 ; and
(b) maintaining the cell for a time sufficient to obtain degradation of the mRNA transcript of the Factor V gene, thereby inhibiting the expression of the Factor V gene in the cell.