The present invention relates to a polynucleotide that comprises at least one phosphorothioate internucleoside linkage and at least one guanosine analogue comprising a guanine nucleobase analogue selected from the group consisting of: formula (I) and formula (II). Polynucleotides comprising such guanosine analogues show a relative reduced neurotoxicity compared to polynucleotides with natural guanosine.

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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.

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 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.

The present invention relates to PIKFYVE antisense oligonucleotides (ASOs), pharmaceutical compositions containing them, and methods for treating, inhibiting, suppressing, and preventing neurological diseases with them.

Provided herein are methods, compounds, and compositions for reducing expression of transthyretin mRNA and protein in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate transthyretin amyloidosis, or a symptom thereof.

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).

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.