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US 11,446,380 B2Granted
Compositions and methods for inhibition of HAO1 (hydroxyacid oxidase 1 (glycolate oxidase)) gene expression
AssigneeAlnylam Pharmaceuticals, Inc.
InventorsWilliam Querbes, Kevin Fitzgerald, Brian Bettencourt, Abigail Liebow, David V. Erbe
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Abstract
The invention relates to RNAi agents, e.g., double-stranded RNAi agents, targeting the HAO1 gene, and methods of using such RNAi agents to inhibit expression of HAO1 and methods of treating subjects having, e.g., PH1.
Claims16
A double stranded RNAi agent, or salt thereof, that inhibits expression of HAO1 in a cell,
- comprising a sense strand and an antisense strand forming a double stranded region, wherein the sense strand comprises the nucleotide sequence of 5′-gsascuuuCfaUfCfCfuggaaauauaL96-3′ (SEQ ID NO:213) and the antisense strand comprises the nucleotide sequence 5′-usAfsuauUfuCfCfaggaUfgAfaagucscsa-3′ (SEQ ID NO:330),
- wherein a, g, c, and u are 2′-O-methyl (2′-OMe) modified A, G, C, and U nucleotides, respectively;
- Af, Gf, Cf, and Uf are 2′ fluoro A, G, C, and U modified nucleotides, respectively;
- s is a phosphorothioate linkage;
- and L96 is N-[tris(GalNAc-alkyl)-amidodecanoyl)]-4-hydroxyprolinol.
2 more elements
A double stranded RNAi agent, or salt thereof, that inhibits expression of HAO1 in a cell,
- comprising a sense strand and an antisense strand forming a double stranded region, wherein the sense strand comprises the nucleotide sequence of 5′-gsascuuuCfaUfCfCfuggaaauaua-3′ (SEQ ID NO:213) and the antisense strand comprises the nucleotide sequence 5′-usAfsuauUfuCfCfaggaUfgAfaagucscsa-3′ (SEQ ID NO:330),
- wherein a, g, c, and u are 2′-O-methyl (2′-OMe) modified A, G, C, and U nucleotides, respectively;
- Af, Gf, Cf, and Uf are 2′ fluoro A, G, C, and U modified nucleotides, respectively;
- and s is a phosphorothioate linkage,
- wherein a ligand is conjugated to the 3′ end of the sense strand as shown in the following schematic
- wherein X is O.
3 more elements
Dependencies are inferred from the claim text.