The present invention provides iRNA agents, e.g., double stranded iRNA agents, that target the transthyretin (TTR) gene and methods of using such iRNA agents for treating or preventing TTR-associated ocular diseases.

This disclosure provides, e.g., novel cells having a modification (e.g., insertion or deletion) in the endogenous CD123 gene. The disclosure also provides compositions, e.g., gRNAs, that can be used to make such a modification.

Disclosed herein are antisense oligonucleotide sequences, and methods of use for treating neurological diseases. Described herein are oligonucleotide inhibitors. In various embodiments, the oligonucleotide targets a transcript for the treatment of neurological diseases, including motor neuron diseases, and/or neuropathies. For example, inhibitors of the transcript can be used to treat PD, ALS, FTD, and ALS with FTD.

The present invention relates to a composition for diagnosing cardio-cerebrovascular disease and a composition for preventing or treating cardio-cerebrovascular disease. The present invention may provide important clinical information that enables early establishment of treatment strategies by highly reliable prediction of not only the development of cardio-cerebrovascular diseases, including arteriosclerosis, but also the likelihood of future development of cardio-cerebrovascular diseases, based on the expression of lncRNA HSPA7. In addition, the composition for treating cardio-cerebrovascular disease according to the present invention inhibits HSPA7 expression, thereby inhibiting the migration of smooth muscle cells and decreasing the expression of inflammatory factors to block the development and progression of atherosclerotic plaques themselves, and thus it may be effectively used as a fundamental therapeutic composition that goes beyond symptomatic therapy such as administration of antithrombotic agents.

The present disclosure relates to extracellular vesicles, e.g., exosomes, comprising an NLRP3 antagonist. In some aspects, the NLRP3 antagonist comprises an antisense oligonucleotide (ASO). Also provided herein are methods for producing the exosomes and methods for using the exosomes to treat and/or prevent diseases or disorders.

The disclosure relates to double stranded ribonucleic acid (dsRNAi) agents and compositions targeting a leucine-rich repeat kinase 2 (LRRK2) gene, as well as methods of inhibiting expression of a LRRK2 gene and methods of treating subjects having a LRRK2-associated disease or disorder, e.g., Parkinson's disease, using such dsRNAi agents and compositions.

The present invention relates to RNAi agents, e.g., double stranded RNA (dsRNA) agents, targeting a Fc fragment of IgG receptor and transporter (FCGRT) gene encoding neonatal Fc receptor (FcRn). The invention also relates to methods of using such RNAi agents to inhibit expression of the FCGRT gene or production of the FcRn protein and to methods of preventing and treating a hepatotoxicity-associated disorder, e.g., alcoholic hepatitis, iron overload, and hepatocellular carcinoma.

Provided herein are compositions and methods for decreasing tau mRNA and protein expression. These compositions and methods are useful in treating tau-related diseases and disorders.

Methods of inhibiting a respiratory virus, (i.e., a virus associated with a respiratory condition, e.g., influenza A, influenza B, RSV, etc.) in a sample are provided. Aspects of the methods include contacting a sample comprising viral RNA (vRNA) having a target motif with an effective amount of an agent that specifically binds the target motif to inhibit the respiratory virus. Also provided are methods of treating or preventing respiratory virus infection in a subject. Also provided are compounds and pharmaceutical compositions comprising an oligonucleotide sequence complementary to a target vRNA region that find use in the subject methods.

Among other things, the present disclosure relates to designed oligonucleotides, compositions, and methods thereof. In some embodiments, provided oligonucleotide compositions provide altered splicing of a transcript. In some embodiments, provided oligonucleotide compositions have low toxicity. In some embodiments, provided oligonucleotide compositions provide improved protein binding profiles. In some embodiments, provided oligonucleotide compositions have improved delivery. In some embodiments, provided oligonucleotide compositions have improved uptake. In some embodiments, the present disclosure provides methods for treatment of diseases using provided oligonucleotide compositions.