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.

Provided herein are methods for decreasing LRRK2 mRNA expression. Such methods are useful to ameliorate LRRK2 associated diseases. Such LRRK2 associated diseases include Parkinson's Disease, including non-LRRK2 mediated Parkinson's Disease.

Provided herein are methods for decreasing LRRK2 mRNA expression. Such methods are useful to ameliorate LRRK2 associated diseases. Such LRRK2 associated diseases include Parkinson's Disease, including non-LRRK2 mediated Parkinson's Disease.

Provided is a single-stranded oligonucleotide that is capable of controlling a target gene with high efficiency and can be easily produced. The single-stranded oligonucleotide is represented by the formula X-L-Y wherein X and Y hybridize by a first nucleotide sequence portion and a second nucleotide sequence portion. X is composed of 7 to 100 nucleotides, contains at least one modified nucleotide, and has a first nucleotide sequence that is capable of hybridizing with a second oligonucleotide and contains at least four contiguous nucleotides recognized by RNase H. Y is composed of 4 to 100 nucleotides, and has a second nucleotide sequence that is capable of hybridizing with a second oligonucleotide and contains at least one ribonucleotide. At least one of nucleotide sequence X and nucleotide sequence Y has an antisense sequence capable of hybridizing with a target RNA. L is a group derived from a third oligonucleotide that is degraded under physiological conditions.

The present description relates to the use of a SRSF3 agent for regulating the function of a myeloid cell, such as a microglial cell and/or monocyte, for treating neurological conditions, cancers, bacterial infections and viral infections wherein the SRSF3 agent inhibits expression or function of SRSF3.

The present description relates to the use of a SRSF3 agent for regulating the function of a myeloid cell, such as a microglial cell and/or monocyte, for treating neurological conditions, cancers, bacterial infections and viral infections wherein the SRSF3 agent inhibits expression or function of SRSF3.

The present disclosure provides oligonucleotide compositions comprising (1) an oligonucleotide of the present disclosure, e.g., an ASO, siRNA, shRNA, DNA or RNA aptamer, gene therapy vector, miRNA, miRNA mimic, antimiR, DNA or RNA decoy, CpG oligonucleotide, or any therapeutic or diagnostic oligonucleotide known in the art, and (ii) a caprylic acid derivative, e.g., 5-CNAC. In some aspects, the oligonucleotide composition is formulated for delivery to the gastrointestinal tract. Thus, some aspects, the present disclosure provides oligonucleotide compositions for oral delivery comprising a therapeutic or diagnostic oligonucleotide (e.g., an ASO) and a caprylic acid derivative (e.g., 5-CNAC or de derivative thereof).

The present disclosure provides oligonucleotide compositions comprising (1) an oligonucleotide of the present disclosure, e.g., an ASO, siRNA, shRNA, DNA or RNA aptamer, gene therapy vector, miRNA, miRNA mimic, antimiR, DNA or RNA decoy, CpG oligonucleotide, or any therapeutic or diagnostic oligonucleotide known in the art, and (ii) a caprylic acid derivative, e.g., 5-CNAC. In some aspects, the oligonucleotide composition is formulated for delivery to the gastrointestinal tract. Thus, some aspects, the present disclosure provides oligonucleotide compositions for oral delivery comprising a therapeutic or diagnostic oligonucleotide (e.g., an ASO) and a caprylic acid derivative (e.g., 5-CNAC or de derivative thereof).

The invention relates to antisense polynucleotide agents targeting the LECT2 gene, and methods of using such antisense polynucleotide agents to inhibit expression of LECT2 and to treat subjects having a LECT2-associated disease, e.g., amyloidosis.

The invention relates to antisense polynucleotide agents targeting the LECT2 gene, and methods of using such antisense polynucleotide agents to inhibit expression of LECT2 and to treat subjects having a LECT2-associated disease, e.g., amyloidosis.