XANTHINE DEHYDROGENASE (XDH) iRNA COMPOSITIONS AND METHODS OF USE THEREOF
AssigneeAlnylam Pharmaceuticals, Inc.
InventorsJames D. McIninch, Jingxuan Liu, Mark K. Schlegel, Adam Castoreno, Anna Borodovsky
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Abstract
The present invention relates to RNAi agents, e.g., dsRNA agents, targeting the xanthine dehydrogenase (XDH) gene. The invention also relates to methods of using such RNAi agents to inhibit expression of an XDH gene and to methods of treating or preventing an XDH-associated disease in a subject.
Claims30
A method of treating a subject having a disorder that would benefit from reduction in xanthine dehydrogenase (XDH) expression, the method comprising administering to the subject a therapeutically effective amount of a double stranded ribonucleic acid (dsRNA) agent comprising a sense strand and an antisense strand forming a double stranded region,
- wherein the sense strand comprises at least 19 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of nucleotides 2701-2721 of SEQ ID NO:
- 1, and the antisense strand comprises at least 19 contiguous nucleotides from the corresponding nucleotide sequence of SEQ ID NO:
- 2,
- wherein all of the nucleotides of the sense strand and all of the nucleotides of the antisense strand are modified nucleotides,
- wherein the sense strand comprises two phosphorothioate internucleotide linkages at the 5′-terminus, and
- wherein the antisense strand comprises two phosphorothioate internucleotide linkages at the 5′-terminus and two phosphorothioate internucleotide linkages at the 3′-terminus.
- thereby treating the subject having the disorder that would benefit from reduction in XDH expression.
The method of 1, wherein the disorder is an XDH-associated disease.
A method of treating a subject having a disorder that would benefit from reduction in xanthine dehydrogenase (XDH) expression, the method comprising administering to the subject a therapeutically effective amount of a double stranded ribonucleic acid (dsRNA) agent comprising a sense strand and an antisense strand forming a double stranded region,
- wherein the sense strand comprises the nucleotide sequence 5′-uscsagagUfaUfUfAfuggaacgagu-3′(SEQ ID NO:853) and the antisense strand comprises the nucleotide sequence 5′-asCfsucgUfuccauaaUfaCfucugasgsa-3′(SEQ ID NO:1212),
- wherein a, g, c, and u are 2′-O-methyl (2′-OMe) A, G, C, and U, respectively;
- Af, Gf, Cf and Uf are 2′-fluoro A, G, C and U, respectively;
- and s is a phosphorothioate linkage;
- and
- wherein the 3′-end of the sense strand is conjugated to a ligand as shown in the following schematic
- wherein X is O,
- thereby treating the subject having the disorder that would benefit from reduction in XDH expression.
Dependencies are inferred from the claim text.