Compositions And Methods For Inhibiting Expression Of CD45 Gene

Abstract

The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of the CD45 gene.

We claim: 
     
         1 . An isolated double-stranded ribonucleic acid (dsRNA), wherein said dsRNA comprises a sense strand and an antisense strand that are substantially complementary to each other and are each 15-30 nucleotides in length, and the antisense strand comprising a region of complementarity that is substantially complementary to an mRNA encoding a CD45. 
     
     
         2 . The dsRNA of  claim 1 , wherein said dsRNA, upon contact with a cell expressing said CD45, inhibits expression of said CD45 by at least 20%. 
     
     
         3 . The dsRNA of  claim 1 , wherein said dsRNA comprises at least one modified nucleotide. 
     
     
         4 . The dsRNA of  claim 3 , wherein said modified nucleotide is chosen from the group consisting 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 consisting 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 . The dsRNA of  claim 1 , wherein said region of complementarity is at least 15 nucleotides in length. 
     
     
         7 . The dsRNA of  claim 1 , wherein said region of complementarity is 19-24 nucleotides in length. 
     
     
         8 . The dsRNA of  claim 1 , wherein said dsRNA, upon contact with a cell expressing CD45, inhibits expression of CD45 by at least 20% as measured in the P388D1 cell assay. 
     
     
         9 . The dsRNA of  claim 1 , wherein said region of complementarity is complementary to at least 15 contiguous nucleotides of one of SEQ ID NOS:97-144. 
     
     
         10 . A cell comprising the dsRNA of  claim 1 . 
     
     
         11 . A pharmaceutical composition comprising the dsRNA of  claim 1 , and a pharmaceutically acceptable carrier. 
     
     
         12 . The pharmaceutical composition of  claim 11 , wherein said dsRNA, upon contact with a cell expressing said CD45 gene, inhibits expression of said CD45 gene by at least 20%, as measured in a P388D1 cell assay. 
     
     
         13 . A method for inhibiting expression of a CD45 gene 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 an mRNA transcript of the CD45 gene, thereby inhibiting expression of the CD45 gene in the cell.   
     
     
         14 . The method of  claim 13 , wherein the cell produced in step (a) is maintained for a time sufficient inhibit expression expression of the CD45 gene by 20%. 
     
     
         15 . A method of treating or managing an autoimmune disease comprising administering to a patient in need of such treatment or management a effective amount of the dsRNA of  claim 1 . 
     
     
         16 . The method of  claim 15 , wherein the autoimmune disease is Graves' disease or multiple sclerosis. 
     
     
         17 . A method of treating or managing a viral infection comprising administering to a patient in need of such treatment or management a therapeutically effective amount of the dsRNA of  claim 1 . 
     
     
         18 . The method of  claim 17 , wherein the infection is caused by a virus of the group consisting of Ebola, influenza, anthrax, hepatitis B and hepatitis C. 
     
     
         19 . A vector for inhibiting the expression of a CD45 gene in a cell, said vector comprising a regulatory sequence operably linked to a nucleotide sequence that encodes at least one strand of the dsRNA of  claim 1 . 
     
     
         20 . A cell comprising the vector of  claim 19 .