MICROTUBULE ASSOCIATED PROTEIN TAU (MAPT) iRNA AGENT COMPOSITIONS AND METHODS OF USE THEREOF

A double stranded ribonucleic acid (dsRNA) agent, or a pharmaceutically acceptable salt thereof, comprising a sense strand and an antisense strand forming a double stranded region, wherein the antisense strand comprises the nucleotide sequence,

• 5′-VPusAfsccdAudAcgagcuUfgGfgucacsgsu-3′ (SEQ ID. NO:
• 1011),
• wherein
• VP is a 5′-vinyl phosphonate;
• s is a phosphorothioate linkage;
• a, c, g, and u are 2′-O-methyl (2′-OMe) A, C, G, and U, respectively;
• dA is 2′-deoxy A;
• and
• Af, Gf, Uf are 2′-deoxy-2′-fluoro (2′-F) A, G, and U, respectively.

A double stranded ribonucleic acid (dsRNA) agent, or a pharmaceutically acceptable salt thereof, comprising a sense strand and an antisense strand forming a double stranded region, wherein the sense strand consists of the nucleotide sequence,

• 5′-gsusgac(Chd)caAfGfCfucguauggsusa-3′ (SEQ ID. NO:
• 1007),
• and the antisense strand consists of the nucleotide sequence,
• 5′-VPusAfsccdAudAcgagcuUfgGfgucacsgsu-3′ (SEQ ID. NO:
• 1011),
• wherein
• VP is a 5′-vinyl phosphonate;
• s is a phosphorothioate linkage;
• a, c, g, and u are 2′-O-methyl (2′-OMe) A, C, G, and U, respectively;
• dA is 2′-deoxy A;
• Af, Cf, Gf, Uf are 2′-deoxy-2′-fluoro (2′-F) A, C, G, and U, respectively;
• and
• (Chd) is 2′-O-hexadecyl-cytidine-3′-phosphate.

A double stranded ribonucleic acid (dsRNA) agent for inhibiting expression of MAPT, wherein the dsRNA agent comprises a sense strand and an antisense strand forming a double stranded region,

• wherein the antisense strand comprises a region of complementarity to an mRNA encoding Tau, and wherein the region of complementarity comprises at least 17 contiguous nucleotides differing at positions except A at position 7 counting from the 5′-end of the antisense sequence, by no more than three nucleotides from the antisense sequence,
• (SEQ ID NO:
• 1003)
• UACCA UACGA GCUUG GGUCA CGU.