Methods and compositions for the specific inhibition of glycolate oxidase (HAO1) by double-stranded RNA

A nucleic acid comprising an oligonucleotide strand of 21-23 nucleotides in length, wherein the oligonucleotide is sufficiently complementary to a target region of HAO1 mRNA having a sequence as set forth in SEQ ID NO:

• 1823 along at least 15 nucleotides of the oligonucleotide strand length to reduce HAO1 target mRNA expression when the nucleic acid is introduced into a cell expressing the HAO1 mRNA, and wherein the nucleic acid comprises one or more modified nucleotides.

A method for treating a subject having primary hyperoxaluria 1 (PHI), the method comprising:

• administering to the subject a nucleic acid comprising a first strand and a second strand forming a duplex structure, wherein the first strand is 21 nucleotides in length and the second strand is 23 nucleotides in length, wherein the second strand is 100% complementary with the sequence as set forth in SEQ ID NO:
• 1823, wherein the second strand has a 3′ overhang of 2 nucleotides in length, wherein a GalNac moiety is conjugated to the 3′ terminal nucleotide of the first strand, and wherein administration of the nucleic acid to the subject results in a reduction of HAO1 mRNA levels in the subject.