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

A method of reducing or preventing kidney damage in a subject having primary hyperoxaluria 1 (PH1), the method comprising administering to the subject a single dose of an effective amount of a double stranded nucleic acid that comprises a first oligonucleotide strand and a second oligonucleotide strand that form a duplex region, wherein the second oligonucleotide strand is sufficiently complementary to a target HAO1 mRNA along at least 15 nucleotides of the oligonucleotide strand length to reduce expression of the HAO1 target mRNA by RNA interference, wherein the first oligonucleotide strand and/or the second oligonucleotide strand comprise one or more modified nucleotides independently selected from 2′-O-methyl modified nucleotides and 2′-fluoro modified nucleotides, and wherein one or more GalNac moieties are conjugated to one or more nucleotides of the first oligonucleotide strand and/or the second oligonucleotide strand, wherein the single dose results in reduction of HAO1 mRNA in the subject that remains detectable at day 29 post administration.