Transmembrane protease, serine 6 (TMPRSS6) iRNA compositions and methods of use thereof

A composition, or a pharmaceutically acceptable salt thereof, comprising a sense strand and an antisense strand,

• wherein the sense strand comprises the nucleotide sequence 5′-asgscugcccUfUfUfggaauaaaguL96-3′ (SEQ ID NO:395) and the antisense strand comprises the nucleotide sequence 5′-asdCsuudTadTuccadAaGfggcagcusgsa-3′ (SEQ ID NO:521),
• wherein a, g, c and u are 2′-O-methyl (2′-OMe) A, G, C, and U, respectively;
• Gf and Uf are 2′-deoxy-2′-fluoro (2′-F) G and U, respectively;
• dC, dA, and dT are 2′-deoxy C, A, and T, respectively;
• and s is a phosphorothioate linkage, and
• wherein L96 is a ligand conjugated to the 3′-end of the sense strand as shown in the following schematic
• wherein X is O.

A composition, or a pharmaceutically acceptable salt thereof, comprising a sense strand and an antisense strand,

• wherein the sense strand consists of the nucleotide sequence 5′-asgscugcccUfUfUfggaauaaaguL96-3′ (SEQ ID N0:395) and the antisense strand consists of the nucleotide sequence 5′-asdCsuudTadTuccadAaGfggcagcusgsa-3′ (SEQ ID NO:521),
• wherein a, g, c and u are 2′-O-methyl (2′-OMe) A, G, C, and U, respectively;
• Gf and Uf are 2′-deoxy-2′-fluoro (2′-F) G and U, respectively;
• dC, dA, and dT are 2′-deoxy C, A, and T, respectively;
• and s is a phosphorothioate linkage, and
• wherein L96 is a ligand conjugated to the 3′-end of the sense strand as shown in the following schematic
• and wherein X is O.

A double stranded ribonucleic acid (dsRNA) agent for inhibiting expression of Transmembrane protease, serine 6 (TMPRSS6) in a cell, or a pharmaceutically acceptable salt thereof, comprising a sense strand and an antisense strand forming a double stranded region,

• wherein the sense strand comprises the nucleotide sequence 5′-asgscugcccUfUfUfggaauaaagu-3′ (SEQ ID N0:395) and the antisense strand comprises the nucleotide sequence 5′-asdCsuudTadTuccadAaGfggcagcusgsa-3′ (SEQ ID NO:521),
• wherein a, g, c and u are 2′-O-methyl (2′-OMe) A, G, C, and U, respectively;
• Gf and Uf are 2′-deoxy-2′-fluoro (2′-F) G and U, respectively;
• dC, dA, and dT are 2′-deoxy C, A, and T, respectively;
• and s is a phosphorothioate linkage, and
• wherein the dsRNA agent is conjugated to a ligand.