COMPOSITIONS AND METHODS FOR INHIBITION OF HAO1 (HYDROXYACID OXIDASE 1 (GLYCOLATE OXIDASE)) GENE EXPRESSION

1 . A double stranded RNAi agent that inhibits expression of HAO1 in a cell, or a salt thereof,

wherein said double stranded RNAi agent or a salt thereof, comprises a sense strand and an antisense strand forming a double-stranded region,

wherein said sense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from any one of the nucleotide sequences of SEQ ID NO:1 SEQ ID NO:2, SEQ ID NO:5, or SEQ ID NO:6 and said antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from any one of the nucleotide sequences of SEQ ID NO:3 SEQ ID NO:4, SEQ ID NO:7, or SEQ ID NO:8;

wherein all of the nucleotides of said sense strand and all of the nucleotides of said antisense strand comprise a nucleotide modification, and

wherein at least one strand is conjugated to a ligand.

2 . (canceled)

3 . (canceled)

4 . The double stranded RNAi agent, or a salt thereof, of claim 1 , wherein at least one of the nucleotide modifications is selected from the group consisting of a 3′-terminal deoxy-thymine (dT) nucleotide modification, a 2′-O-methyl nucleotide modification, a 2′-fluoro nucleotide modification, a 2′-deoxy-nucleotide modification, a locked nucleotide modification, an abasic nucleotide modification, a 2′-amino-nucleotide modification, a 2′-alkyl-nucleotide modification, a morpholino nucleotide modification, a phosphoramidate modification, a non-natural base comprising nucleotide modification, a nucleotide comprising a 5′-phosphorothioate group modification, a nucleotide comprising a 5′ phosphate or 5′ phosphate mimic modification, and a terminal nucleotide linked to a cholesteryl derivative or a dodecanoic acid bisdecylamide group modification.

5 . The double stranded RNAi agent, or a salt thereof, of claim 1 , wherein at least one strand comprises a 3′ overhang of at least 1 nucleotide.

6 . The double stranded RNAi agent, or a salt thereof, of claim 1 , wherein at least one strand comprises a 3′ overhang of at least 2 nucleotides.

7 .- 17 . (canceled)

18 . The double stranded RNAi agent, or a salt thereof, of claim 1 , wherein the double-stranded region is 15-30 nucleotide pairs in length.

19 .- 23 . (canceled)

24 . The double stranded RNAi agent, or a salt thereof, of claim 1 , wherein each strand is 15-30 nucleotides in length.

25 .- 27 . (canceled)

28 . The double stranded RNAi agent, or a salt thereof, of claim 1 , wherein the ligand is one or more GalNAc derivatives attached through a bivalent or trivalent branched linker.

29 . The double stranded RNAi agent, or a salt thereof, of claim 1 , wherein the ligand is

30 . The double stranded RNAi agent, or a salt thereof, of claim 1 , wherein the ligand is attached to the 3′ end of the sense strand.

31 . The double stranded RNAi agent, or a salt thereof, of claim 30 , wherein the RNAi agent is conjugated to the ligand as shown in the following schematic

wherein X is O or S.

32 . The double stranded RNAi agent, or a salt thereof, of claim 1 , wherein said agent further comprises at least one phosphorothioate or methylphosphonate internucleotide linkage.

33 .- 40 . (canceled)

41 . The double stranded RNAi agent, or a salt thereof, of claim 32 , wherein said RNAi agent comprises 6-8 phosphorothioate internucleotide linkages.

42 .- 55 . (canceled)

56 . A double stranded RNAi agent that inhibits expression of HAO1 in a cell, or a salt thereof,

wherein said double stranded RNAi agent, or a salt thereof, comprises a sense strand and an antisense strand forming a double stranded region,

wherein said sense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from any one of the nucleotide sequences of from any one of the nucleotide sequences of SEQ ID NO:1 SEQ ID NO:2, SEQ ID NO:5, or SEQ ID NO:6 and said antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from any one of the nucleotide sequences of SEQ ID NO:3 SEQ ID NO:4, SEQ ID NO:7, or SEQ ID NO:8,

wherein all of the nucleotides of said sense strand comprise a modification selected from the group consisting of a 2′-O-methyl modification and a 2′-fluoro modification,

wherein said sense strand comprises two phosphorothioate internucleotide linkages at the 5′-terminus,

wherein all of the nucleotides of said antisense strand comprise a modification selected from the group consisting of a 2′-O-methyl modification and a 2′-fluoro modification,

wherein said antisense strand comprises two phosphorothioate internucleotide linkages at the 5′-terminus and two phosphorothioate internucleotide linkages at the 3′-terminus, and

wherein said sense strand is conjugated to one or more GalNAc derivatives attached through a branched bivalent or trivalent linker at the 3′-terminus.

57 .- 66 . (canceled)

67 . A cell containing the double stranded RNAi agent, or a salt thereof, of claim 1 .

68 . A pharmaceutical composition comprising the double stranded RNAi agent, or a salt thereof, of claim 1 .

69 .- 73 . (canceled)

74 . A method of inhibiting HAO1 expression in a cell, the method comprising:

(a) contacting the cell with the double stranded RNAi agent, or a salt thereof, of claim 1 ; and

(b) maintaining the cell produced in step (a) for a time sufficient to obtain degradation of the mRNA transcript of a HAO1 gene, thereby inhibiting expression of the HAO1 gene in the cell.

75 .- 81 . (canceled)

82 . A method of treating a subject having a HAO1 associated disorder, comprising administering to the subject a therapeutically effective amount of the double stranded RNAi agent, or a salt thereof, of claim 1 , thereby treating said subject.

83 . (canceled)

84 . (canceled)

85 . The method of claim 82 , wherein the subject is a human.

86 . The method of claim 85 , wherein the human has PH1.

87 .- 89 . (canceled)

90 . The method of claim 87 , wherein the double stranded RNAi agent or a salt thereof, is administered to the subject subcutaneously.

91 .- 94 . (canceled)