RNAs, such as miRNA and siRNA, and their use in treating complement-mediated disorders, are described.

A double stranded RNA interference (RNAi) agent comprising at least one of (i) a first double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of a CD320 gene wherein the first dsRNA comprises a sense strand and an antisense strand forming a duplex, (ii) a second dsRNA for inhibiting the expression of a LRP2 gene wherein the second dsRNA comprises a sense strand and an antisense strand forming a duplex, or (iii) a cocktail of (i) and (ii) and wherein the sense strand of the first dsRNA is at least substantially complementary to the antisense strand of the first dsRNA and the sense strand of the second dsRNA is at least substantially complementary to the antisense strand of the second dsRNA and the use of the RNAi agent as a pharmaceutical composition for the treatment of cancer in subjects in need of treatment.

The present invention relates to nucleic acid molecules that are complementary to both PAP associated domain containing 5 (PAPD5) and PAP associated domain containing 7 (PAPD7), leading to inhibition of the expression of both PAPD5 and PAPD7 when using a single nucleic acid molecule. The invention also provides for PAPD5 and PAPD7 specific nucleic acid molecules for use in treating and/or preventing a HBV infection, in particular a chronic HBV infection. Also comprised in the present invention is a pharmaceutical composition for use in the treatment and/or prevention of a HBV infection.

The present invention relates to RNAi agents, e.g., double stranded RNA (dsRNA) agents, targeting the Patatin-Like Phospholipase Domain Containing 3 (PNPLA3) gene. The invention also relates to methods of using such RNAi agents to inhibit expression of a PNPLA3 gene and to methods of preventing and treating an PNPLA3-associated disorder, e.g., Nonalcoholic Fatty Liver Disease (NAFLD).

This disclosure relates to novel SYNGR-3 targeting sequences. Novel SYNGR-3 targeting oligonucleotides for the treatment of neurodegenerative diseases are also provided.

The present invention relates to RNAi constructs for reducing expression of the LPA gene, which encodes apolipoprotein(a), a component of lipoprotein(a) (Lp(a)) particles. Methods of using such RNAi constructs to treat or prevent cardiovascular disease, such as coronary artery disease, peripheral artery disease, stroke, and myocardial infarction, and to reduce serum Lp(a) levels are also described.

Among other things, the present disclosure provides designed oligonucleotides, compositions, and methods thereof. In some embodiments, provided oligonucleotide compositions provide improved single-stranded RNA interference and/or RNase H-mediated knockdown. Among other things, the present disclosure encompasses the recognition that structural elements of oligonucleotides, such as base sequence, chemical modifications (e.g., modifications of sugar, base, and/or internucleotidic linkages) or patterns thereof, conjugation with additional chemical moieties, and/or stereochemistry [e.g., stereochemistry of backbone chiral centers (chiral internucleotidic linkages)], and/or patterns thereof, can have significant impact on oligonucleotide properties and activities, e.g., RNA interference (RNAi) activity, stability, delivery, etc. In some embodiments, the present disclosure provides methods for treatment of diseases using provided oligonucleotide compositions, for example, in RNA interference and/or RNase H-mediated knockdown.

The disclosure relates to double stranded ribonucleic acid (dsRNAi) agents and compositions targeting a leucine-rich repeat kinase 2 (LRRK2) gene, as well as methods of inhibiting expression of a LRRK2 gene and methods of treating subjects having a LRRK2-associated disease or disorder, e.g., Parkinson's disease, using such dsRNAi agents and compositions.

The present invention relates to RNAi agents, e.g., double stranded RNA (dsRNA) agents, targeting the mannan binding lectin serine peptidase 2 gene (MASP2). The invention also relates to methods of using such RNAi agents to inhibit expression of a MASP2 gene and to methods of preventing and treating a MASP2-associated disorders, e.g., arthritis, IgA nephropathy, thrombotic microangiopathy, diabetic nephropathy and membranous nephropathy.

The present invention relates to RNAi agents, e.g., double stranded RNA (dsRNA) agents, targeting a Fc fragment of IgG receptor and transporter (FCGRT) gene encoding neonatal Fc receptor (FcRn). The invention also relates to methods of using such RNAi agents to inhibit expression of the FCGRT gene or production of the FcRn protein and to methods of preventing and treating a hepatotoxicity-associated disorder, e.g., alcoholic hepatitis, iron overload, and hepatocellular carcinoma.