Abstract: The present disclosure provides oligomeric compounds (including oligomeric compounds that are antisense agents or portions thereof) comprising a modified oligonucleotide having at least one modified intemucleoside linkage. In some embodiments, the disclosure provides oligomeric compounds and modified oligonucleotides comprising a central region in which purine-containing central region nucleosides are adjacent to methanesulfonyl phosphoramidate intemucleoside linkages.

Abstract: Provided are oligomeric compounds, methods, and pharmaceutical compositions for modulating expression of SCN1A RNA and/or protein in a cell or subject. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom of a developmental or epileptic encephalopathic disease, such as, for example, Dravet Syndrome. Such symptoms include seizures, sudden unexpected death in epilepsy, status epilepticus, behavioral dysfunctions, movement and balance dysfunctions, orthopedic conditions, motor dysfunctions, cognitive impairment, delayed language and speech, visual motor integration dysfunctions, visual perception dysfunctions, executive dysfunctions, and dysautonomia.

Abstract: Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of LRRK2 RNA in a cell or animal, and in certain instances reducing the amount of LRRK2 protein in a cell or animal. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom or hallmark of a neurodegenerative disease. Such symptoms and hallmarks include ataxia, neuropathy, and aggregate formation. Such neurodegenerative diseases include Parkinson's disease.

Abstract: Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of UBE3A-ATS, the endogenous antisense transcript of ubiquitin protein ligase E3A (UBE3A) in a cell or subject, and in certain instances increasing the expression of paternal UBE3A and the amount of UBE3A protein in a cell or subject. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom or hallmark of a neurogenetic disorder. Such symptoms and hallmarks include developmental delays, ataxia, speech impairment, sleep problems, seizures, and EEG abnormalities. Such neurogenetic disorders include Angelman Syndrome.

Abstract: The present embodiments provide compounds and methods for targeting cells expressing GLP-1 receptor.

Abstract: Provided are compounds, pharmaceutical compositions, and methods of use for reducing the amount or activity of DUX4 RNA in a cell or animal, and in certain instances reducing the amount of DUX4 protein in a cell or animal. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom or hallmark of a muscular dystrophy. Such symptoms and hallmarks include muscle weakness and/or muscle wasting in facio, scapula, and/or humeral muscle that can progress to the muscles of the trunk and/or lower limbs. Such muscular dystrophies include Facioscapulohumeral muscular dystrophy (FSHD).

Abstract: 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.

Abstract: Disclosed herein are antisense compounds and methods for selectively reducing expression of an allelic variant of a gene containing a single nucleotide polymorphism (SNP). Such methods, compounds, and composition are useful to treat, prevent, or ameliorate diseases, including neurodegenerative diseases, such as Huntington's Disease (HD).

Abstract: Provided herein are compounds, pharmaceutical compositions, and methods of use for selectively reducing the amount or activity of HTT RNA comprising SNP rs7685686 in a cell or subject, and in certain instances reducing the amount of mutant HTT protein in a cell or subject. Such compounds, pharmaceutical compositions, and methods of use are useful to ameliorate at least one symptom or hallmark of Huntington's disease.

Abstract: Provided are compounds, methods, and pharmaceutical compositions for increasing the amount or activity of STMN2 RNA in a cell or animal, and in certain embodiments increasing the amount of STMN2 protein in a cell or animal. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom of a neurodegenerative disease. Such symptoms include ataxia, neuropathy, synaptic dysfunction, deficits in cognition, and decreased longevity. Such neurodegenerative diseases include amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer's disease (AD), and dementia with Lewy bodies (DLB).

Abstract: 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.

Abstract: Disclosed herein are antisense compounds and methods for decreasing Ataxin 2 mRNA and protein expression. Such methods, compounds, and compositions are useful to treat, prevent, or ameliorate Ataxin 2 associated diseases, disorders, and conditions. Such Ataxin 2 associated diseases include spinocerebellar ataxia type 2 (SCA2), amyotropic sclerosis (ALS), and parkinsonism.

Abstract: Disclosed herein are antisense compounds and methods for selectively reducing expression of an allelic variant of a huntingtin gene containing a single nucleotide polymorphism (SNP). Such methods, compounds, and composition are useful to treat, prevent, or ameliorate Huntington's Disease (HD).

Abstract: Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of ATXN3 RNA in a cell or animal, and in certain embodiments reducing the amount of ATXN3 protein in a cell or animal. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom or hallmark of a neurodegenerative disease. Such symptoms and hallmarks include motor dysfunction, aggregation formation, and neuron death. Such neurodegenerative diseases include spinocerebellar ataxia type 3(SCA3).

Abstract: Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of APP RNA in a cell or a subject, and in certain instances reducing the amount of APP protein in a cell or a subject. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom or hallmark of a neurodegenerative disease or disorder associated with APP. Such symptoms and hallmarks include cognitive impairment, including a decline in memory and language skills, behavioral and psychological symptoms such as apathy and lack of motivation, gait disturbances, seizures, progressive dementia, and abnormal amyloid deposits.

Abstract: Provided are oligomeric compounds and pharmaceutical compositions for increasing the amount or activity of UNC13A RNA in a cell or animal, and/or decreasing the amount of UNC13A RNA that includes a cryptic exon in a cell or animal, and in certain instances increasing the amount of UNC13A protein in a cell or animal. Such oligomeric compounds and pharmaceutical compositions are useful to treat neurodegenerative diseases such as amyotrophic lateral sclerosis and frontotemporal dementia.

Abstract: Provided herein are methods, antisense agents, specific inhibitors, and compositions useful for reducing expression or activity of NADPH oxidase 4 (hereinafter referred to as NOX4) in a subject. Also, provided herein are methods, antisense agents, specific inhibitors, and compositions that can be useful in treating NOX4-related diseases or conditions in a subject. Such methods, antisense agents, specific inhibitors, and compositions can be useful, for example, to treat a pulmonary disease in a subject.

Abstract: The present disclosure 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. In certain embodiments, certain oligomeric compounds selectively reduce the expression of a target nucleic acid transcript relative to a non-target nucleic acid transcript.

Abstract: The present disclosure provides methods of synthesizing modified oligonucletodies and oligomeric compounds (including oligomeric compounds that are antisense agents or portions thereof) comprising a modified oligonucleotide having at least one modified internucleoside linking group. In certain embodiments, the present disclosure provides stabilized formulations of certain sulfonyl azides for use in the synthesis of olignonucleotides comprising one or more sulfonyl phosphoramidate linkages. Some embodiments provide stabilized compositions of high energy reagents that may be used in the synthesis of modified oligonucleotides, allowing for safe process scale preparation thereof.

Abstract: 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.