Methods and compositions for the specific inhibition of glycolate oxidase (HAO1) by double-stranded RNA
AssigneeDicerna Pharmaceuticals, Inc.
InventorsBob D. Brown, Henryk T. Dudek
Life of this patent
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Abstract
This invention relates to compounds, compositions, and methods useful for reducing Glycolate Oxidase (HAO1) target RNA and protein levels via use of dsRNAs, e.g., Dicer substrate siRNA (DsiRNA) agents.
Claims38
A nucleic acid comprising an oligonucleotide strand of 19-80 nucleotides in length, wherein said oligonucleotide strand is complementary to SEQ ID NO:
- 1823 along at least 19 consecutive nucleotides of said oligonucleotide strand length and reduces HAO1 target mRNA expression when said nucleic acid is introduced into a mammalian cell, wherein the nucleic acid comprises one or more modified nucleotides.
A double stranded nucleic acid (dsNA) comprising first and second nucleic acid strands, wherein said first strand is 15-66 nucleotides in length and said second strand of said dsNA is 19-66 nucleotides in length, wherein said second strand is complementary to SEQ ID NO:
- 1823 along at least 19 consecutive nucleotides of said second oligonucleotide strand length and reduces HAO1 target mRNA expression when said double stranded nucleic acid is introduced into a mammalian cell, wherein the dsNA comprises one or more modified nucleotides.
A double stranded nucleic acid (dsNA) comprising first and second nucleic acid strands and a duplex region of at least 25 base pairs, wherein said first strand is 25-65 nucleotides in length and said second strand of said dsNA is 26-66 nucleotides in length and comprises 1-5 single-stranded nucleotides at its 3′ terminus, wherein said second strand is complementary to SEQ ID NO:
- 1823 along at least 19 consecutive nucleotides of said second oligonucleotide strand length and reduces HAO1 target gene expression when said double stranded nucleic acid is introduced into a mammalian cell, wherein the dsNA comprises one or more modified nucleotides.
A double stranded nucleic acid (dsNA) comprising first and second nucleic acid strands and a duplex region of at least 25 base pairs, wherein said first strand is 25-65 nucleotides in length and said second strand of said dsNA is 26-66 nucleotides in length and comprises 1-5 single-stranded nucleotides at its 3′ terminus, wherein the 3′ terminus of said first strand and the 5′ terminus of said second strand form a blunt end, and said second strand is complementary to SEQ ID NO:
- 1823 along at least 19 nucleotides of said second oligonucleotide strand length and reduces HAO1 mRNA expression when said double stranded nucleic acid is introduced into a mammalian cell, wherein the dsNA comprises one or more modified nucleotides.
A dsNA comprising a first strand and a second strand, wherein the first strand and the second strand form a duplex region of 19-25 nucleotides in length, wherein the first strand comprises a 3′ region that extends beyond the first strand-second strand duplex region and comprises a tetraloop, and the dsNA further comprises a discontinuity between the 3′ terminus of the first strand and the 5′ terminus of the second strand, and the first or second strand is complementary to SEQ ID NOs:
- NO:
- 1823 along at least 19 consecutive nucleotides of the first or second strand length and reduces HAO1 target mRNA expression when the dsNA is introduced into a mammalian cell, wherein the dsNA comprises one or more modified nucleotides.
Dependencies are inferred from the claim text.