Abstract: The present invention provides methods for the treatment of non-alcoholic steatohepatitis (NASH) including advanced fibrotic and/or cirrhotic stages of NASH. The methods include administration of a compound comprising a double stranded RNAi (dsRNAi) oligonucleotide, or a pharmaceutically acceptable salt thereof, to the patient. The dsRNAi oligonucleotide optionally contains an antisense strand and a sense strand, wherein the antisense strand and the sense strand form a duplex region, and wherein the antisense strand comprises a region of complementarity to a KHK mRNA target sequence.

Abstract: dsRNAi oligonucleotides can be used in methods for the treatment of NASH, preferably the advanced fibrotic and/or cirrhotic stages thereof, using dosage regimens comprising a loading phase followed by a maintenance phase.

Abstract: The subject matter disclosed herein is directed to modulating gene expression using siRNA compositions and methods directed to affecting key cell populations supporting the growth and metastasis of cancer to affect the beneficial treatment, remission or removal of the underlying tumor in a patient.

Abstract: This invention relates to compounds, compositions, and methods useful for reducing ?-1 antitrypsin target RNA and protein levels via use of dsRNAs, e.g., Dicer substrate siRNA (DsiRNA) agents.

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.

Abstract: Oligonucleotides are provided herein that inhibit MAPT gene expression, including oligonucleotides conjugated to a targeting ligand (e.g., lipid moiety). Also provided are compositions including the same and uses thereof, particularly uses relating to treating diseases, disorders, and/or conditions associated with MAPT gene expression.

Abstract: Oligonucleotides (e.g., RNAi oligonucleotides) are provided herein that inhibit SNCA gene expression, including oligonucleotides conjugated to a targeting ligand (e.g., GalNAC moiety or lipid moiety). Also provided are compositions including the same and uses thereof, particularly uses relating to treating diseases, disorders, and/or conditions associated with SNCA gene expression.

Abstract: This disclosure relates to chemically modified oligonucleotides, compositions, and methods useful for reducing ALDH2 expression, to treat alcoholism. Disclosed oligonucleotide for the reduction of ALDH2 expression is modified for enhanced pharmacological properties.

Abstract: This invention relates to compounds, compositions, and methods useful for reducing ?-1 antitrypsin target RNA and protein levels via use of dsRNAs, e.g., Dicer substrate siRNA (DsiRNA) agents.

Abstract: Oligonucleotides and compositions including the same are disclosed that modulate (e.g., inhibit, limit or reduce) sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP) activity. Methods of making and using the oligonucleotides also are disclosed, particularly uses relating to treating diseases, disorders, and/or conditions associated with SCAP activity such as nonalcoholic fatty liver disease (NAFLD), (NASH), dyslipidemia, atherosclerotic cardiovascular disease (ASCVD), and/or other SCAP-associated conditions, diseases, and/or disorders.

Abstract: This disclosure relates to oligonucleotides, compositions and methods useful for reducing GYS2 expression, particularly in hepatocytes. Disclosed oligonucleotides for the reduction of GYS2 expression may be double-stranded or single-stranded, and may be modified for improved characteristics such as stronger resistance to nucleases and lower immunogenicity. Disclosed oligonucleotides for the reduction of GYS2 expression may also include targeting ligands to target a particular cell or organ, such as the hepatocytes of the liver, and may be used to treat glycogen storage diseases (e.g., GSDIa, GSDIII, GSDIV, GSDVI, and GSDIX) and related conditions.

Abstract: This invention relates to compounds, compositions, and methods useful for reducing C5 target RNA and protein levels via use of dsRNAs, e.g., Dicer substrate siRNA (DsiRNA) agents.

Abstract: Oligonucleotides are provided herein that inhibit angiopoietin-like protein 3 (ANGPTL3) expression. Also provided are compositions including the same and uses thereof, particularly uses relating to treating diseases, disorders and/or conditions associated with ANGPTL3 expression.

Abstract: This disclosure relates to oligonucleotides, compositions and methods useful for reducing PCSK9 expression, particularly in hepatocytes. Disclosed oligonucleotides for the reduction of PCSK9 expression may be double-stranded or single-stranded, and may be modified for improved characteristics such as stronger resistance to nucleases and lower immunogenicity. Disclosed oligonucleotides for the reduction of PCSK9 expression may also include targeting ligands to target a particular cell or organ, such as the hepatocytes of the liver, and may be used to treat hypercholesterolemia, atherosclerosis, and/or one or more symptoms or complications thereof.

Abstract: This invention relates to compounds, compositions, and methods useful for reducing transthyretin (TTR) target RNA and protein levels via use of dsRNAs, e.g., Dicer substrate siRNA (DsiRNA) agents.

Abstract: This invention relates to compounds, compositions, and methods useful for reducing AT3 target RNA and protein levels via use of dsRNAs, e.g., Dicer substrate siRNA (DsiRNA) agents.

Abstract: This disclosure relates to oligonucleotides, compositions and methods useful for reducing LDHA expression, particularly in hepatocytes.

Abstract: This invention relates to compounds, compositions, and methods useful for reducing ?-1 antitrypsin target RNA and protein levels via use of dsRNAs, e.g., Dicer substrate siRNA (DsiRNA) agents.

Abstract: This invention relates to compounds, compositions, and methods useful for reducing transthyretin (TTR) target RNA and protein levels via use of dsRNAs, e.g., Dicer substrate siRNA (DsiRNA) agents.

Abstract: This disclosure relates to oligonucleotides, compositions and methods useful for reducing GYS2 expression, particularly in hepatocytes. Disclosed oligonucleotides for the reduction of GYS2 expression may be double-stranded or single-stranded, and may be modified for improved characteristics such as stronger resistance to nucleases and lower immunogenicity. Disclosed oligonucleotides for the reduction of GYS2 expression may also include targeting ligands to target a particular cell or organ, such as the hepatocytes of the liver, and may be used to treat glycogen storage diseases (e.g., GSDIa, GSDIII, GSDIV, GSDVI, and GSDIX) and related conditions.