The present invention is directed to compositions and methods for treating hepatitis B virus infection. In particular, the present invention is directed to a combination therapy comprising administration of a therapeutic oligonucleotide targeting HBV and a TLR7 agonist for use in the treatment of a chronic hepatitis B patient.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload inhibits activity of a pro-atrophy gene. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

A cross-linked nucleoside of the present invention is a compound represented by the formula (I) below. The cross-linked nucleoside of the present invention is usable as a substitute for a phosphorothioate-modified nucleic acid, which has a risk of, for example, accumulation in a specific organ. The cross-linked nucleoside also has excellent industrial productivity.

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The present disclosure provides oligomeric compound comprising a modified oligonucleotide having a central region comprising one or more modifications. In certain embodiments, the present disclosure provides oligomeric compounds having an improved therapeutic index or an increased maximum tolerated dose.

Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of KCNQ2 RNA in a cell or subject, and in certain instances reducing the amount of K.sub.v7.2 protein in a cell or subject. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom or hallmark of an epileptic encephalopathy. Such symptoms and hallmarks include infantile spasms or seizures, EEC abnormalities, brain MRI abnormalities in the infant, and an associated developmental impairment. Such epileptic encephalopathies include those associated with gain-of-function and dominant negative mutations in KCNQ2.

Provided herein are methods, compounds, and compositions for reducing expression of an ANGPTL3 mRNA and protein in an animal. Also provided herein are methods, compounds, and compositions for reducing lipids and/or glucose in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate any one or more of cardiovascular disease and/or metabolic disease, or a symptom thereof, in an individual in need thereof.

Provided herein are methods, compounds, and compositions for reducing expression of an ANGPTL3 mRNA and protein in an animal. Also provided herein are methods, compounds, and compositions for reducing lipids and/or glucose in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate any one or more of cardiovascular disease and/or metabolic disease, or a symptom thereof, in an individual in need thereof.

The present invention relates to antisense LNA oligonucleotides (oligomers) complementary to ATXN3 pre-mRNA sequences, which are capable of inhibiting the expression of ATXN3 protein. Inhibition of ATXN3 expression is beneficial for the treatment of spinocerebellar ataxia.

Disclosed is a method of treating a subject who has a neurological disease. In one aspect, the method includes a step of administering an effective dose of a SYF2 antisense or inhibitory nucleic acid to a subject in need thereof, thereby restoring nuclear localization of TDP-43.

The present disclosure features useful compositions and methods to treat nucleotide repeat expansion disorders, e.g., in a subject in need thereof. In some aspects, the compositions and methods described herein are useful in the treatment of disorders associated with MSH3 activity.