Dicerna Pharmaceuticals, Inc.

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.

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.

This application relates to potent oligonucleotides useful for reducing HBsAg expression and treating HBV infections.

Oligonucleotides are provided herein that inhibit apolipoprotein(a) (LPA) expression. Also provided are compositions including the same and uses thereof, particularly uses relating to treating diseases, disorders and/or conditions associated with LPA expression.

This application relates to potent oligonucleotides useful for reducing HBsAg expression and treating HBV infections.

The invention provides for double stranded nucleic acid molecules comprising a 5′extension of the sense or antisense strand and further comprising a plurality of nucleotides that are conjugated to a ligand and methods of using the double-stranded nucleic acid molecules. Ligand-modified oligomers where the sense stands form a tetraloop provide new potent and stable RNA interference agents. These dsNA molecules are synthesized using a plurality of nucleotides that include ligand-modified monomers, nucleotide analog monomers, modified nucleotide monomers and the like, using standard nucleotide synthetic methods and systems.

The disclosure provides methods for synthesis of peracetylgalactosamine-1-pentanoic acid, also called peracetylated D-galactosamine C5 linker or GalNAc C5 linker, using a vegetal source as a starting material, such as vegetal-sourced D-glucosamine or D-glucosamine hydrochloride. Also provided are methods for purifying the peracetylgalactosamine-1-pentanoic acid, or GalNAc C5 linker, thus produced so that the end product comprises fewer impurities.

Oligonucleotides are provided herein that inhibit apolipoprotein(a) (LPA) expression. Also provided are compositions including the same and uses thereof, particularly uses relating to treating diseases, disorders and/or conditions associated with LPA expression.

Oligonucleotides and compositions including the same are disclosed for inhibiting or reducing apolipoprotein C-III (APOC3) gene expression. Methods of making and using the oligonucleotides also are disclosed, particularly uses relating to treating diseases, disorders and/or conditions associated with APOC3 expression.

The present invention relates to the preparation of nucleic acids, nucleosides, nucleotides, and analogues thereof useful as potent and stable RNA interference agents. The present invention provides improved yields and avoids the use of lead tetraacetate for decarboxylative acetylation which decreases the overall cost of production by removing the need for lead remediation and offers a significant reduction in the environmental costs in production.