Provided herein are methods, compounds, and compositions for reducing expression of GYS1 in an individual. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate a glycogen storage disease or disorder in an individual in need.

The present disclosure provides methods of identifying non-productive splice sites in target RNA transcripts and antisense oligonucleotides that increase the expression of said target RNA transcripts. In an embodiment, the target RNA transcript comprises ADAR, ARSA, ATPIA2, CACNAIA, DNMI, EIF2BI, EIF2B2, EIF2B5, IDUA, MFSD8, NF2, NPC1L PEXI, PRICKLE2, PRRT2, RAM, SETD5, SHANKS, SLC6A1, STXBPI, STX1B, and TCF4.

Provided are oligomeric compounds, methods, and pharmaceutical compositions for reducing the amount or activity of IFNAR1 RNA in a cell or animal, and in certain instances reducing the amount of IFNAR1 protein in a cell or animal Such oligomeric compounds, methods, and pharmaceutical compositions are useful to treat diseases and conditions associated with neuroinflammation, including Aicardi-Goutières Syndrome, stroke, neuropsychiatric systemic lupus erythematosus, neuroinflammation following traumatic brain injury, neuro-autoimmune disorders, Alzheimer's disease, post-operative delirium and cognitive decline, cranial radiation-induced cognitive decline, viral infection-induced cognitive decline, neuromyelitis optica, and ataxia telangiectasia.

The present disclosure relates to modified extracellular vesicles, e.g., exosomes, comprising an antisense oligonucleotide (ASO), which is capable of reducing and/or inhibiting expression of KRAS mRNA and/or KRAS protein. ASOs that can be used with the modified extracellular vesicles are also disclosed. Also provided herein are methods for using the exosomes and ASOs to treat and/or prevent diseases, such as cancer.

Disclosed herein are methods for decreasing AlAT mRNA and protein expression and treating, ameliorating, preventing, slowing progression, or stopping progression of fibrosis. Disclosed herein are methods for decreasing A1AT mRNA and protein expression and treating, ameliorating, preventing, slowing progression, or stopping progression of liver disease, such as, A1ATD associated liver disease, and pulmonary disease, such as, A1ATD associated pulmonary disease in an individual in need thereof. Methods for inhibiting AlAT mRNA and protein expression can also be used as a prophylactic treatment to prevent individuals at risk for developing a liver disease, such as, A1ATD associated liver disease and pulmonary disease, such as, A1ATD associated pulmonary disease.

The present disclosure relates to compositions of oligonucleotide (e.g., SMAD7 antisense oligonucleotide diastereomers) and methods of manufacturing, assessing efficacy, and using the compositions.

An object of the present invention is to provide a lipid composition capable of achieving excellent nucleic acid delivery. According to the present invention, there is provided a lipid composition containing a lipid represented by Formula (1) or a salt thereof, a nucleic acid, at least one non-cationic lipid, and a lipid represented by R.sup.51-L-(OCH.sub.2CH.sub.2).sub.n—O-R.sup.52 (in the formula, R.sup.51 represents a hydrocarbon group having 6 to 30 carbon atoms, L represents —CO— or a single bond, R.sup.52 represents a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, and n represents an integer of 10 to 150).

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In the formula, each symbol means the definition described in the description.

The present embodiments provide methods, compounds, and compositions useful for inhibiting FOXP3 expression, which may be useful for treating, preventing, or ameliorating cancer.

Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of FXII RNA in a cell or subject, and in certain instances reducing the amount of FXII protein in a cell or subject. Such compounds, methods, and pharmaceutical compositions are useful to prevent, treat, or ameliorate at least one symptom of a thromboembolic condition. Such thromboembolic conditions include deep vein thrombosis, venous or arterial thrombosis, pulmonary embolism, myocardial infarction, and stroke. Such symptoms include pain, shortness of breath, heart burn, cold sweat, fatigue, lightheadedness, dizziness, swelling, cramping, and death. Such compounds, methods, and pharmaceutical compositions are useful to prevent, treat, or ameliorate at least one symptom of hereditary angioedema.

The present disclosure relates to immunostimulatory compositions that are effective in eliciting immune responses in avian species. More specifically, these immunostimulatory compositions comprise an immunomodulator composition and an immunostimulatory oligonucleotide that when administered stimulate toll-like receptor 21.