Modulation of tmprss6 expression

Abstract

Disclosed herein are antisense compounds and methods for modulating TMPRSS6 and modulating an iron accumulation disease, disorder and/or condition in an individual in need thereof. Iron accumulation diseases in an individual such as hemochromatosis or β-thalassemia can be ameliorated or prevented with the administration of antisense compounds targeted to TMPRSS6.

1 - 39 . (canceled) 
     
     
         40 . A compound comprising a modified oligonucleotide consisting of 12 to 30 linked nucleosides, wherein at least 12 consecutive nucleobases of the modified oligonucleotide are at least 85% identical to an equal length portion of SEQ ID NO: 8 or SEQ ID NO: 9. 
     
     
         41 . The compound of  claim 40 , wherein at least 12 consecutive nucleobases of the modified oligonucleotide are at least 85% identical to an equal length portion of SEQ ID NO: 8. 
     
     
         42 . The compound of  claim 40 , wherein at least 12 consecutive nucleobases of the modified oligonucleotide are at least 85% identical to an equal length portion of SEQ ID NO: 9. 
     
     
         43 . The compound of  claim 40 , wherein the modified oligonucleotide nucleobase sequence is at least 90% complementary to SEQ ID NO. 1. 
     
     
         44 . The compound of  claim 40 , wherein the modified oligonucleotide is single stranded. 
     
     
         45 . The compound of  claim 40 , wherein the modified oligonucleotide comprises:
 a gap segment consisting of linked deoxynucleosides;   a 5′ wing segment consisting of linked nucleosides; and   a 3′ wing segment consisting of linked nucleosides;   
       wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment and wherein each nucleoside of each wing segment comprises a modified sugar. 
     
     
         46 . The compound of  claim 45 , wherein the modified sugar is a 2′-O-methoxyethyl modified sugar. 
     
     
         47 . The compound of  claim 40 , wherein at least one internucleoside linkage is a phosphorothioate internucleoside linkage. 
     
     
         48 . The compound of  claim 40 , wherein at least one nucleoside comprises a modified nucleobase. 
     
     
         49 . The compound of  claim 48 , wherein the modified nucleobase is a 5-methyl cytosine. 
     
     
         50 . The compound of  claim 40 , wherein the modified oligonucleotide comprises a modified sugar selected from a 2′-O-methoxyethyl modified sugar and a 2′-O-methyl modified sugar. 
     
     
         51 . The compound of  claim 40 , wherein the modified oligonucleotide comprises a modified sugar selected from a constrained ethyl, a LNA, and a 3′-fluoro-HNA. 
     
     
         52 . The compound of  claim 40 , wherein the modified oligonucleotide consists of 20 linked nucleosides. 
     
     
         53 . The compound of  claim 52 , wherein the modified oligonucleotide has a nucleobase sequence of SEQ ID NO: 8. 
     
     
         54 . The compound of  claim 52 , wherein the modified oligonucleotide has a nucleobase sequence of SEQ ID NO: 9. 
     
     
         55 . The compound of  claim 40 , wherein the compound consists essentially of the modified oligonucleotide. 
     
     
         56 . The compound of  claim 40 , wherein the compound comprises a conjugate group linked to the modified oligonucleotide. 
     
     
         57 . The compound of  claim 56 , wherein the compound consists essentially of the conjugate group and the modified oligonucleotide. 
     
     
         58 . A method comprising contacting a cell with the compound of  claim 41 . 
     
     
         59 . A method comprising contacting a cell with the compound of  claim 42 .