The invention relates to nucleic acid products that interfere with complement component C3 gene expression or inhibit its expression. The nucleic acids are preferably for use as treatment, prevention or reduction of risk of suffering from complement component C3 associated diseases, disorders or syndromes, particularly C3 Glomerulopathy (C3G), Paroxysmal Nocturnal Hemoglobinuria (PNH), atypical Hemolytic Uremic Syndrome (aHUS), Lupus nephritis, IgA nephropathy (IgA N), Cold Agglutinin Disease (CAD), Myasthenia gravis (MG), and Primary Membranous Nephropathy.

The present invention provides oligonucleotides for use in the treatment of hepatitis B or hepatitis B virus infection in a human patient.

Provided herein are compositions and methods for inducing CRISPR/Cas-based editing of a target nucleic acid (e.g., target DNA or target RNA), or modulating the express of a target nucleic acid, in vitro or in a cell, using modified guide RNAs (gRNAs) that incorporate one or more chemically-modified nucleotides. In some aspects, these modified gRNAs provide superior performance under challenging conditions.

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.

Novel oligonucleotides that enhance silencing of the expression of a gene containing a single nucleotide polymorphism (SNP) relative to the expression of the corresponding wild-type gene are provided. Methods of using novel oligonucleotides that enhance silencing of the expression of a gene containing a SNP relative to the expression of the corresponding wild-type gene are provided.

The invention relates to nucleic acid products that interfere with or inhibit PROS1 gene expression. It further relates to therapeutic uses of PROS1 inhibition for the treatment of bleeding disorders.

Therapeutic oligonucleotides comprising pharmacokinetic (PK)-modifying anchors are provided. Methods for treating diseases or disorders comprising administering to a subject a therapeutic oligonucleotide comprising one or more PK-modifying anchors are provided.

Novel oligonucleotides that are fully chemically stabilized are provided. Methods of using oligonucleotides that are fully chemically stabilized are also provided.

One aspect of the present invention relates to an oral formulation for reducing or inhibiting the expression of a target gene in a subject, comprising a) double stranded iRNA agent comprising an antisense strand which is complementary to a target gene; a sense strand which is complementary to said antisense strand; 2′-OMe modifications to more than fifteen, more than twenty, more than twenty-five, or more than thirty nucleotides; and a carbohydrate-based ligand conjugated to at least one strand, optionally via a linker or carrier; and b) a penetration enhancer. Another aspect of the invention relates to a method of gene silencing, comprising orally administering to a subject in need thereof the oral formulation.

The invention relates to a single-stranded antisense gapmer oligonucleotide comprising at least one dinucleoside of formula (I)

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wherein (A.sup.1), (A.sup.2) and A are as defined in the description and in the claims. The oligonucleotide according to the invention can be used as a medicament.