Therapeutic oligonucleotides comprising pharmacokinetic (PK)-modifying anchors are provided. Methods for treating diseases or disorders comprising administering to a subject a therapeutic oligonucleotide comprising one or more PK-modifying anchors are provided.

The invention relates to double stranded ribonucleic acid (dsRNAi) agents and compositions targeting the SCAP gene, as well as methods of inhibiting expression of a SCAP gene and methods of treating subjects having a SCAP-associated disorder, such as nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH), using such dsRNAi agents and compositions.

The present disclosure provides antisense compounds, methods, and compositions for silencing ADAM33 mRNA. The present disclosure provides antisense compounds, methods, and compositions for the treatment, prevention, or amelioration of diseases, disorders, and conditions associated with ADAM33 in a subject in need thereof. Also contemplated are antisense compounds and methods for the preparation of a medicament for the treatment, prevention, or amelioration of a disease, disorder, or condition associated with ADAM33.

Amphiphilic oligonucleotide conjugates that enhance adjuvant function are disclosed. The conjugates typically include: a lipophilic component, and conjugated thereto (directly or indirectly) an immunomodulating oligonucleotide that, if it were not conjugated to the lipophilic component, would suppress TLR7 and/or TLR8 stimulation. In the presence of albumin, these conjugates significantly enhance adjuvant function, in particular the function of TLR7/8-mediated adjuvants such as an imidazoquinolinamine. The conjugates can be administered, along with an adjuvant compound, to a subject in order to cause and/or enhance an immune response (for instance, to an infectious agent or a cancer antigen) in the subject.

Provided herein are compositions and methods of use for mimicking miRNA activity. For example, these compositions can be effective in modulating expression of pro-inflammatory mediators, such as NLRP3. The compositions can be useful for treating musculoskeletal or connective tissue repair or degenerative conditions, for example, tendinopathy and tendon injury.

The invention relates to saRNA targeting an HNF4a transcript and therapeutic compositions comprising said saRNA. Methods of using the therapeutic compositions are also provided.

The disclosure relates to double stranded ribonucleic acid (dsRNAi) agents and compositions targeting an RPS25 gene, as well as methods of inhibiting expression of an RPS25 gene and methods of treating subjects having an RPS25-associated disease or disorder, such as a nucleotide repeat expansion disorder, e.g., c9orf72 amyotrophic lateral sclerosis (ALS)/frontotemporal demential (FTD) and Huntington-Like Syndrome Due To C9orf72 Expansions, using such dsRNAi agents and compositions.

Disclosed herein are antisense compounds and methods for decreasing PKK mRNA and protein expression. Such methods, compounds, and compositions are useful to treat, prevent, or ameliorate PKK-associated diseases, disorders, and conditions.

The invention relates to a double-stranded ribonucleic acid (dsRNA) targeting a G-alpha q subunit (GNAQ) of a heterotrimeric G gene, and methods of using the dsRNA to inhibit expression of GNAQ.

Compositions related to spherical nucleic acids (SNAs) with antisense oligonucleotides and methods of treatment of diseases and disorders are disclosed therein. In particular, the antisense oligonucleotides are targeted to a region in a pre-mRNA of interest to regulate pre-mRNA splicing.