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 the Factor V Leiden mutant gene (Factor V Leiden mutant gene), 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 the Factor V Leiden mutant gene. 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 the Factor V Leiden mutant gene using the pharmaceutical composition; and methods for inhibiting the expression of the Factor V Leiden mutant gene in a cell.
1. An isolated double-stranded ribonucleic acid (dsRNA), wherein said dsRNA comprises a sense strand and an antisense strand and wherein said sense strand consists of the nucleotide sequence of SEQ ID NO:1 (5′-CCCUGGACAGGCGAGGAAUTT-3′) and said antisense strand consists of the nucleotide sequence of SEQ ID NO:2 (5′-AUUCCUCGCCUGUCCAGGGTT-3′).
2. The dsRNA of claim 1 , wherein said dsRNA comprises at least one modified nucleotide.
3. The dsRNA of claim 2 , 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.
4. 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.
5. An isolated cell comprising the dsRNA of claim 1 .
6. A pharmaceutical composition comprising the dsRNA of claim 1 and a pharmaceutically acceptable carrier.
7. A vector comprising a regulatory sequence operably linked to a nucleotide sequence that encodes at least one strand of the dsRNA of claim 1 .
8. A cell comprising the vector of claim 7 .
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.