Described herein are compositions and methods for treating Alzheimer's disease or dementia. The compositions include mammalian suppressor of taupathy 2 inhibitors (MSUT2). The MSUT2 inhibitors can be small interfering RNAs, guide RNAs, or small molecules. The methods include reducing accumulation of phosphorylated and aggregated human tau.

Described herein are compositions and methods for treating Alzheimer's disease or dementia. The compositions include mammalian suppressor of taupathy 2 inhibitors (MSUT2). The MSUT2 inhibitors can be small interfering RNAs, guide RNAs, or small molecules. The methods include reducing accumulation of phosphorylated and aggregated human tau.

A method of promoting the generation of oligodendrocytes from oligodendrocyte precursor cells by enhancing their survival and/or maturation includes administering to the cell an effective amount of an agent that enhances and/or induces accumulation of Δ8,9-unsaturated sterol intermediates of the cholesterol biosynthesis pathway in the oligodendrocyte precursor cells.

A method of promoting the generation of oligodendrocytes from oligodendrocyte precursor cells by enhancing their survival and/or maturation includes administering to the cell an effective amount of an agent that enhances and/or induces accumulation of Δ8,9-unsaturated sterol intermediates of the cholesterol biosynthesis pathway in the oligodendrocyte precursor cells.

Methods and compositions for modulating repeat non-ATG protein (RAN protein) translation are provided. In some aspects, the disclosure provides methods of inhibiting RAN protein translation by contacting a cell with an effective amount of an inhibitor of eIF2 phosphorylation or an inhibitor of protein kinase R (PKR). In some embodiments, methods described by the disclosure are useful for treating diseases associated with RAN protein translation, such as certain neurodegenerative diseases.

Methods and compositions for modulating repeat non-ATG protein (RAN protein) translation are provided. In some aspects, the disclosure provides methods of inhibiting RAN protein translation by contacting a cell with an effective amount of an inhibitor of eIF2 phosphorylation or an inhibitor of protein kinase R (PKR). In some embodiments, methods described by the disclosure are useful for treating diseases associated with RAN protein translation, such as certain neurodegenerative diseases.

This application relates to potent oligonucleotides useful for reducing HBsAg expression and treating HBV infections.

This application relates to potent oligonucleotides useful for reducing HBsAg expression and treating HBV infections.

Provided are a UV light-responsive hyperbranched poly-(β-amino ester having high-efficiency gene delivery ability and a preparation method and application thereof; said poly-β-amino ester uses 4-amino-1-butanol, 2-nitro-1, M-phthaloyl 3-diacrylate, trimethylolpropane triacrylate, and 1-(3-aminopropyl)-4-methylpiperazine as raw materials, is polymerized by means of the “A2+B3+C2” Michael addition method, causing it to have a hyperbranched structure. In comparison with a linear structure, the branched structure enhances the interaction between the polymer and the nucleic acid molecule, significantly improving gene condensation ability, while also increasing cellular uptake by means of enhancing the interaction with the cell membrane. The poly-(β-amino ester has a UV-responsive group on the backbone chain; under UV light irradiation, the poly-(β-amino ester can be rapidly degraded after endocytosis, and releases the encapsulated genes, and achieves efficient gene transfection and reduces material toxicity. The invention has good prospects for development in the field of biomedical materials, and particularly in gene delivery.

Provided are a UV light-responsive hyperbranched poly-(β-amino ester having high-efficiency gene delivery ability and a preparation method and application thereof; said poly-β-amino ester uses 4-amino-1-butanol, 2-nitro-1, M-phthaloyl 3-diacrylate, trimethylolpropane triacrylate, and 1-(3-aminopropyl)-4-methylpiperazine as raw materials, is polymerized by means of the “A2+B3+C2” Michael addition method, causing it to have a hyperbranched structure. In comparison with a linear structure, the branched structure enhances the interaction between the polymer and the nucleic acid molecule, significantly improving gene condensation ability, while also increasing cellular uptake by means of enhancing the interaction with the cell membrane. The poly-(β-amino ester has a UV-responsive group on the backbone chain; under UV light irradiation, the poly-(β-amino ester can be rapidly degraded after endocytosis, and releases the encapsulated genes, and achieves efficient gene transfection and reduces material toxicity. The invention has good prospects for development in the field of biomedical materials, and particularly in gene delivery.