Compositions and methods for inhibiting expression of patatin-like phospholipase domain-containing 3 (pnpla3)
AssigneeShanghai Argo Biopharmaceutical Co., Ltd.
InventorsDongxu Shu, Shiwei Xia
Life of this patent
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Abstract
Compositions and methods useful to reduce expression of Patatin-like Phospholipase Domain Containing 3 (PNPLA3) gene and for treatment of PNPLA3-associated diseases and conditions are provided. Provided are PNPLA3 dsRNA agents, PNPLA3 antisense polynucleotide agents, compositions comprising PNPLA3 dsRNA agents, and compositions comprising PNPLA3 antisense polynucleotide agents that can be used to reduce PNPLA3 expression in cells and subjects.
Claims35
A double-stranded ribonucleic acid (dsRNA) agent for inhibiting expression of Patatin-like Phospholipase Domain Containing 3 (PNPLA3), wherein the dsRNA agent includes a sense strand and an antisense strand, wherein the sense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO:
- 1 and the antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from the nucleotide sequence of SEQ ID NO:2, wherein the sense strand and the antisense strand can be partially, substantially, or fully complementary to each other, and optionally comprising a targeting ligand.
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A double-stranded ribonucleic acid (dsRNA) agent for inhibiting expression of Patatin-like Phospholipase Domain Containing 3 (PNPLA3), wherein the dsRNA agent including a sense strand and an antisense strand, wherein the sense strand is complementary to the antisense strand, wherein the antisense strand comprises a region complementary to part of an mRNA encoding PNPLA3, wherein each strand is about 15 to about 30 nucleotides in length, wherein the sense strand sequence is represented by formula (I):
- wherein:
- each N′F represents a 2′-fluoro-modified nucleotide;
- each of N′N1, N′N2, N′N3, N′N4, N′N5, N′N6, N′N7 and N′N8 independently represents a modified or unmodified nucleotide;
- each N′L independently represents a modified or unmodified nucleotide but not a 2′-fluoro-modified nucleotide, and m′ and n′ are each independently an integer of 0 to 7.
A double-stranded ribonucleic acid (dsRNA) agent for inhibiting expression of Patatin-like Phospholipase Domain Containing 3 (PNPLA3), wherein the dsRNA agent including a sense strand and an antisense strand, wherein the sense strand is complementary to the antisense strand, wherein the antisense strand comprises a region complementary to part of an mRNA encoding PNPLA3, wherein each strand is about 18 to about 30 nucleotides in length, wherein the antisense strand sequence is represented by formula (II):
- wherein:
- each NF represents a 2′-fluoro-modified nucleotide;
- each of NM1, NM2, NM3, NM4, NM5, NM6, NM7 and NM8 independently represents a modified or unmodified nucleotide, preferably, NM1, NM2, NM3, NM6 and NM7 each independently represents a 2′-fluoro-modified nucleotide;
- each NL independently represents a modified or unmodified nucleotide but not a 2′-fluoro-modified nucleotide, and n is an integer of 0 to 7.
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Dependencies are inferred from the claim text.