Compositions and Methods for Inhibiting Expression of Eg5 Gene

Abstract

The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of the Eg5 gene (Eg5 gene), comprising an antisense strand having a nucleotide sequence which is less that 30 nucleotides in length, generally 19-25 nucleotides in length, and which is substantially complementary to at least a part of the Eg5 gene. The invention also relates to a pharmaceutical composition comprising the dsRNA together with a pharmaceutically acceptable carrier; methods for treating diseases caused by Eg5 expression and the expression of the Eg5 gene using the pharmaceutical composition; and methods for inhibiting the expression of the Eg5 gene in a cell.

1 . A composition comprising a double-stranded ribonucleic acid (dsRNA) for inhibiting expression of a human kinesin family member 11 (Eg5) gene in a cell, wherein the dsRNA comprises a sense strand comprising a first sequence and an antisense strand comprising a second sequence complementary to the sequence provided in an even SEQ ID NO: 2-580 or an odd SEQ ID NO: 583-1257, wherein the first sequence is complementary to the second sequence and wherein the dsRNA is between 15 and 30 base pairs in length. 
     
     
         2 . The composition of  claim 1 , wherein the dsRNA comprises at least one modified nucleotide. 
     
     
         3 . The composition of  claim 2 , wherein the 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 composition of  claim 2 , wherein the 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 . The composition of  claim 2 , wherein the first dsRNA comprises at least one 2′-O-methyl modified ribonucleotide and at least one phosphorothioate. 
     
     
         6 . The composition of  claim 1 , wherein the composition, upon contact with a cell expressing Eg5, inhibits expression of Eg5 gene by at least 40%. 
     
     
         7 . The composition of  claim 1 , wherein the dsRNA is 19-21 base pairs in length. 
     
     
         8 . An isolated cell comprising the composition of  claim 1 . 
     
     
         9 . A vector comprising a regulatory sequence operably linked to a nucleotide sequence that encodes at least one strand of the dsRNA of the composition of  claim 1 . 
     
     
         10 . An isolated cell comprising the vector of  claim 9 . 
     
     
         11 . A pharmaceutical composition for inhibiting Eg5 gene expression comprising the composition of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         12 . A method for inhibiting Eg5 gene expression in a cell, the method comprising:
 introducing into the cell the composition of  claim 1 ; and   maintaining the cell for a time sufficient to obtain degradation of the mRNA transcript of the Eg5 gene, thereby inhibiting expression of the Eg5 gene in the cell.   
     
     
         13 . A method of treating pathological processes mediated by human Eg5 expression comprising administering to a patient a therapeutically effective amount of the composition of  claim 1 .