Compositions and Methods for Inhibiting Expression of a Gene from the Ebola Virus

Abstract

The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of a gene from the Ebola virus.

We claim: 
     
         1 . A double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of a human Ebola genome in a cell, wherein said dsRNA comprises at least two sequences that are complementary to each other and wherein a sense strand comprises a first sequence and an antisense strand comprises a second sequence comprising a region of complementarity which is substantially complementary to at least a part of a mRNA encoding Ebola, and wherein said region of complementarity is less than 30 nucleotides in length. 
     
     
         2 . The dsRNA of  claim 1 , wherein said first sequence is selected from the group consisting of the sense sequences of Table 2 and said second sequence is selected from the group consisting of the antisense sequences of Table 2. 
     
     
         3 . The dsRNA of  claim 1 , wherein said dsRNA comprises at least one modified nucleotide. 
     
     
         4 . The dsRNA of  claim 2 , wherein said dsRNA comprises at least one modified nucleotide. 
     
     
         5 . The dsRNA of  claims 3 , wherein said modified nucleotide is chosen from the group of: a 2′-0-methyl modified nucleotide, a nucleotide comprising a 5′-phosphorothioate group, and a terminal nucleotide linked to a cholesteryl derivative or dodecanoic acid bisdecylamide group. 
     
     
         6 . 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. 
     
     
         7 . The dsRNA of  claims 3 , wherein said first sequence is selected from the group consisting of the sense sequences of Table 2 and said second sequence is selected from the group consisting of the antisense sequences of Table 2. 
     
     
         8 . The dsRNA of  claim 6 , wherein said first sequence is selected from the group consisting of the sense sequences of Table 2 and said second sequence is selected from the group consisting of the antisense sequences of Table 2. 
     
     
         9 . A cell comprising the dsRNA of  claim 1 . 
     
     
         10 . A pharmaceutical composition for inhibiting the expression of a gene from an Ebola virus in an organism, comprising a dsRNA of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         11 . The pharmaceutical composition of  claim 10 , wherein said first sequence of said dsRNA is selected from the group consisting of the sense sequences of Table 2 and said second sequence is selected from the group consisting of the antisense sequences of Table 2. 
     
     
         12 . The-pharmaceutical composition of  claim 10 , wherein said first sequence of said dsRNA consists of the sequence of SEQ ID NO:1029, and said second sequence consists of the sequence of SEQ ID NO:1030. 
     
     
         13 . A method for inhibiting the expression of a gene from an Ebola virus in a cell, the method comprising:
 (a) introducing into the cell a 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 a gene from the Ebola virus, thereby inhibiting expression of a gene from the Ebola virus in the cell.   
     
     
         14 . A method of treating, preventing or managing pathological processes mediated by Ebola expression comprising administering to a patient in need of such treatment, prevention or management a therapeutically or prophylactically effective amount of a dsRNA of  claim 1 . 
     
     
         15 . A vector for inhibiting the expression of a gene from the Ebola virus in a cell, said vector comprising a regulatory sequence operably linked to a nucleotide sequence that encodes the dsRNA of  claim 1 . 
     
     
         16 . A cell comprising the vector of  claim 15 . 
     
     
         17 . The dsRNA of  claim 1 , wherein the dsRNA targets the VP35 of Ebola. 
     
     
         18 . The dsRNA of  claim 1 , wherein the dsRNA has a sense strand consisting of the sequence of SEQ ID NO:1029, and antisense strand consisting of the sequence of SEQ ID NO:1030. 
     
     
         19 . The dsRNA of  claim 1 , wherein said dsRNA, upon contact with a cell infected with Ebola virus, inhibits expression of a gene from the virus by at least 40%. 
     
     
         20 . The dsRNA of  claim 1 , wherein said region of complementarity is 15-30 nucleotides in length.