Disclosed herein are antisense compounds and methods for decreasing PKK mRNA and protein expression. Such methods, compounds, and compositions are useful to treat, prevent, or ameliorate PKK-associated diseases, disorders, and conditions.

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

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.

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 promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.

The present invention provides oligomeric compounds. Certain such oligomeric compounds are useful for hybridizing to a complementary nucleic acid, including but not limited, to nucleic acids in a cell. In certain embodiments, hybridization results in modulation of the amount activity or expression of the target nucleic acid in a cell.

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.

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 are oligomeric compounds, methods, and pharmaceutical compositions for DMPK the amount or activity of DMPK RNA in a cell or animal, and in certain instances reducing the amount of DMPK protein in a cell or animal. Such oligomeric compounds, methods, and pharmaceutical compositions are useful to treat type 1 myotonic dystrophy.

Provided herein are methods of administering ISIS 721744 for ameliorating edema, and methods of reducing prekallikrein (PKK) RNA, protein or activity in a human subject in need thereof. In certain instances, methods are useful for ameliorating at least one symptom of hereditary angioedema. Such symptoms of hereditary angioedema include, but are not limited to, nausea, vomiting, itching, headache, fatigue, abdominal pain, shortness of breath, rhinitis, anaphylaxis, bronchoconstriction, and swelling. In certain instances, methods are useful for ameliorating at least one symptom of macular edema. Such symptoms of macular edema include, but are not limited to, impaired vision and vision loss.