Transthyretin (TTR) iRNA compositions and methods of use thereof
AssigneeAlnylam Pharmaceuticals, Inc.
InventorsMark K. Schlegel, Adam Castoreno, James D. McIninch
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Abstract
The present invention relates to RNAi agents, e.g., double stranded RNA (dsRNA) agents, targeting the transthyretin (TTR) gene. The invention also relates to methods of using such RNAi agents to inhibit expression of an TTR gene and to methods of preventing and treating an TTR-associated disorder, e.g., senile systemic amyloidosis (SSA), systemic familial amyloidosis, familial amyloidotic polyneuropathy (FAP), familial amyloidotic cardiomyopathy (FAC), leptomeningeal/Central Nervous System (CNS) amyloidosis, and hyperthyroxinemia.
Claims30
A double stranded ribonucleic acid (dsRNA) agent, or salt thereof, for inhibiting expression of transthyretin (TTR) in a cell,
- wherein the dsRNA agent comprises a sense strand and an antisense strand forming a double stranded region,
- wherein the nucleotide sequence of the sense strand differs by no more than 4 bases from the nucleotide sequence 5′-csasagagUfaUfUfCfcauuuuuacu-3′ of SEQ ID NO:
- 21 and the nucleotide sequence of the antisense strand differs by no more than 4 bases from the nucleotide sequence 5′-asGfsuaaAfaauggaaUfaCfucuugsgsu-3′ of SEQ ID NO:
- 22,
- wherein a, c, g, and u are 2′-O-methyl (2′-OMe) A, C, G, and U, respectively;
- Af, Cf, Gf and Uf are 2′-fluoro A, C, G and U, respectively;
- s is a phosphorothioate linkage, and wherein at least one strand is conjugated to a ligand.
A double stranded ribonucleic acid (dsRNA) agent, or salt thereof, for inhibiting expression of transthyretin (TTR) in a cell,
- wherein the dsRNA agent comprises a sense strand and an antisense strand forming a double stranded region,
- wherein the sense strand comprises the nucleotide sequence 5′-csasagagUfaUfUfCfcauuuuuacu-3′ of SEQ ID NO:
- 21 and the antisense strand comprises the nucleotide sequence 5′-asGfsuaaAfaauggaaUfaCfucuugsgsu-3′ of SEQ ID NO:
- 22,
- wherein a, c, g, and u are 2′-O-methyl (2′-OMe) A, C, G, and U, respectively;
- Af, Cf, Gf and Uf are 2′-fluoro A, C, G and U, respectively;
- s is a phosphorothioate linkage, and wherein at least one strand is conjugated to a ligand.
A double stranded ribonucleic acid (dsRNA) agent, or salt thereof, for inhibiting expression of transthyretin (TTR) in a cell,
- wherein the dsRNA agent comprises a sense strand and an antisense strand forming a double stranded region,
- wherein the sense strand comprises the nucleotide sequence 5′-csasagagUfaUfUfCfcauuuuuacu-3′ of SEQ ID NO:
- 21 and the antisense strand comprises the nucleotide sequence 5′-asGfsuaaAfaauggaaUfaCfucuugsgsu-3′ of SEQ ID NO:
- 22,
- wherein a, c, g, and u are 2′-O-methyl (2′-OMe) A, C, G, and U, respectively;
- Af, Cf, Gf and Uf are 2′-fluoro A, C, G and U, respectively;
- s is a phosphorothioate linkage, and wherein the dsRNA agent is conjugated to a ligand as shown in the following schematic
- wherein X is O.
Dependencies are inferred from the claim text.