The present invention relates to a SARAF inhibitor for use in treatment of an HBV infection, in particular a chronic HBV infection. The invention in particular relates to the use of SARAF inhibitors for destabilizing cccDNA, such as HBV cccDNA. The invention also relates to nucleic acid molecules which are complementary to SARAF and capable of reducing the level of a SARAF mRNA. Also comprised in the present invention is a pharmaceutical composition and its use in the treatment of a HBV infection.

The present invention relates to a SCAMP3 inhibitor for use in treatment of an HBV infection, in particular a chronic HBV infection. The invention in particular relates to the use of SCAMP3 inhibitors for destabilizing cccDNA, such as HBV cccDNA. The invention also relates to nucleic acid molecules which are complementary to SCAMP3 and capable of reducing the level of a SCAMP3 mRNA. Also comprised in the present invention is a pharmaceutical composition and its use in the treatment of a HBV infection.

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 modulating splicing of a pre-mRNA in a cell or subject. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom of a disease or disorder.

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.

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.

The present disclosure provides antisense compounds, methods, and compositions for silencing C9ORF72 transcripts. The present disclosure provides antisense compounds, methods, and compositions for the treatment, prevention, or amelioration of diseases, disorders, and conditions associated with C9ORF72 in a subject in need thereof. Also contemplated are antisense compounds and methods for the preparation of a medicament for the treatment, prevention, or amelioration of a disease, disorder, or condition associated with C9ORF72.

Provided are methods for increasing the amount or activity of FMR1 RNA, and in certain instances of increasing the amount of FMRP protein, in an animal Such methods are useful to prevent or ameliorate at least one symptom of a Fragile X-Spectrum disorder. Such Fragile X-Spectrum disorders include FXS, FXTAS, and FXPOI.

The present disclosure provides compounds comprising modified oligonucleotides for use in CRISPR. In certain embodiments, such modified oligonucleotides provide improved properties of crRNA. In certain embodiments, such modified oligonucleotides provide improved properties of scrRNA.