Compositions and methods for inhibiting expression of tmprss6 gene

Abstract

The invention relates to double-stranded ribonucleic acid (dsRNA) compositions targeting the TMPRSS6 gene, and methods of using such dsRNA compositions to inhibit expression of TMPRSS6.

1 . A double-stranded ribonucleic acid (dsRNA) for inhibiting expression of TMPRSS6, wherein said dsRNA comprises a sense strand and an antisense strand, the antisense strand comprising a region of complementarity to a TMPRSS6 transcript which comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from one of the antisense sequences listed in Tables 2, 3 or 4. 
     
     
         2 . The dsRNA of  claim 1 , wherein said dsRNA comprises at least one modified nucleotide. 
     
     
         3 . The dsRNA of  claim 2 , wherein at least one of said modified nucleotides 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. 
     
     
         4 . The dsRNA of  claim 2 , 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. 
     
     
         5 . The dsRNA of  claim 1 , wherein the region of complementarity is at least 17 nucleotides in length. 
     
     
         6 . The dsRNA of  claim 1 , wherein the region of complementarity is between 19 and 21 nucleotides in length. 
     
     
         7 . (canceled) 
     
     
         8 . The dsRNA of  claim 1 , wherein each strand is no more than 30 nucleotides in length. 
     
     
         9 . The dsRNA of  claim 1 , wherein at least one strand comprises a 3′ overhang of at least 1 nucleotide or at least 2 nucleotides. 
     
     
         10 . (canceled) 
     
     
         11 . The dsRNA of  claim 1 , further comprising a ligand. 
     
     
         12 . The dsRNA of  claim 11 , wherein the ligand is conjugated to the 3′ end of the sense strand of the dsRNA. 
     
     
         13 . The dsRNA of  claim 1 , wherein the region of complementarity consists of one of the antisense sequences of Tables 2, 3 or 4. 
     
     
         14 . The dsRNA of  claim 1 , wherein the dsRNA comprises a sense strand consisting of a sense strand sequence selected from Tables 2, 3 or 4 and an antisense strand consisting of an antisense sequence selected from Tables 2, 3 or 4. 
     
     
         15 . A cell containing the dsRNA of  claim 1 . 
     
     
         16 . A pharmaceutical composition for inhibiting expression of a TMPRSS6 gene comprising the dsRNA of  claim 1 . 
     
     
         17 . The pharmaceutical composition of  claim 16 , further comprising a lipid formulation. 
     
     
         18 . (canceled) 
     
     
         19 . A method of inhibiting TMPRSS6 expression 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 TMPRSS6 gene, thereby inhibiting expression of the TMPRSS6 gene in the cell.   
     
     
         20 . (canceled) 
     
     
         21 . A method of treating a disorder mediated by TMPRSS6 expression comprising administering to a human in need of such treatment a therapeutically effective amount of the dsRNA of  claim 1 . 
     
     
         22 .- 26 . (canceled) 
     
     
         27 . A vector encoding at least one strand of a dsRNA, wherein said dsRNA comprises a region of complementarity to at least a part of an mRNA encoding TMPRSS6, wherein said dsRNA is 30 base pairs or less in length, and wherein said dsRNA targets said mRNA for cleavage. 
     
     
         28 .- 31 . (canceled)