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

Abstract

The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of a gene from the JC Virus (JC virus genome), 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 a gene from the JC Virus. The invention also relates to a pharmaceutical composition comprising the dsRNA together with a pharmaceutically acceptable carrier; methods for treating diseases caused by JC virus expression and the expression of a gene from the JC Virus using the pharmaceutical composition; and methods for inhibiting the expression of a gene from the JC Virus in a cell.

1 . A double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of a human JC virus 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 an mRNA encoding the JC virus, and wherein said region of complementarity is less than 30 nucleotides in length and wherein said dsRNA, upon contact with a cell expressing the JC virus, inhibits expression of the JC virus genome. 
     
     
         2 . The dsRNA of  claim 1 , wherein the first sequence is selected from the group consisting of Tables 1a and b and the second sequence is selected from the group consisting of Tables 1a and b. 
     
     
         3 . The dsRNA of  claim 1 , wherein the dsRNA comprises at least one modified nucleotide. 
     
     
         4 . The dsRNA of  claim 2 , wherein the dsRNA comprises at least one modified nucleotide. 
     
     
         5 . The dsRNA of  claim 3 , 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. 
     
     
         6 . The dsRNA of  claim 3 , 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. 
     
     
         7 . The dsRNA of  claim 3 , wherein the first sequence is selected from the group consisting of Tables 1a and b and said second sequence is selected from the group consisting of Tables 1a and b. 
     
     
         8 . The dsRNA of  claim 6 , wherein the first sequence is selected from the group consisting of Tables 1a and b and the second sequence is selected from the group consisting of Tables 1a and b. 
     
     
         9 . A cell comprising the dsRNA of  claim 1 . 
     
     
         10 . A pharmaceutical composition for inhibiting the expression of a gene from the JC Virus in an organism, comprising the dsRNA of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         11 . The pharmaceutical composition of  claim 10 , wherein the first sequence of said dsRNA is selected from the group consisting of Tables 1a and b and the second sequence of the dsRNA is selected from the group consisting of Tables 1a and b. 
     
     
         12 . The pharmaceutical composition of  claim 10 , wherein said first sequence of the dsRNA is selected from the group consisting of Tables 1a and b and the second sequence of said dsRNA is selected from the group consisting of Tables 1a and b. 
     
     
         13 . A method for inhibiting the expression of a gene from a JC Virus in a cell, the method comprising:
 (a) introducing into the cell the 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 JC Virus, thereby inhibiting expression of a gene from the JC Virus in the cell.   
     
     
         14 . A method of treating or preventing pathological processes mediated by JC virus expression comprising administering to a patient in need of such treatment or prevention a therapeutically or prophylactically effective amount of the dsRNA of  claim 1 . 
     
     
         15 . A vector for inhibiting the expression of a gene from the JC Virus in a cell, the vector comprising a regulatory sequence operably linked to a nucleotide sequence that encodes at least one strand of the dsRNA of  claim 1 . 
     
     
         16 . A cell comprising the vector of  claim 15 .