The present invention is related to a ribonucleic acid comprising a double stranded structure whereby the double-stranded structure comprises a first strand and a second strand, whereby the first strand comprises a first stretch of contiguous nucleotides and whereby said first stretch is at least partially complementary to a target nucleic acid, and the second strand comprises a second stretch of contiguous nucleotides whereby said second stretch is at least partially identical to a target nucleic acid, and whereby the double stranded structure is blunt ended.

Described are RNAi agents, compositions that include RNAi agents, and methods for inhibition of a beta-ENaC (SCNN1B) gene. The beta-ENaC RNAi agents and RNAi agent conjugates disclosed herein inhibit the expression of a beta-ENaC gene. Pharmaceutical compositions that include one or more beta-ENaC RNAi agents, optionally with one or more additional therapeutics, are also described. Delivery of the described beta-ENaC RNAi agents to epithelial cells, such as pulmonary epithelial cells, in vivo, provides for inhibition of beta-ENaC gene expression and a reduction in ENaC activity, which can provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases including chronic obstructive pulmonary disease (COPD).

Disclosed herein are polynucleic acid molecules, pharmaceutical compositions, and methods for treating Facioscapulohumeral muscular dystrophy.

Polynucleotide constructs are disclosed, that are potent activators of a STING-independent DNA sensing pathway (SIDSP), in which the DNA damage response protein DNA-PK is the sensor of the SIDSP, along with tire heat shock protein HSPA8 as a unique SIDSP target. The polynucleotide constructs of the disclosure are also potent activators of the cGAS-STING DNA sensing pathway. These pathways arm key components of the innate immune response that is important for antiviral immunity, contributes to specific autoimmune diseases, and mediate important aspects of antitumor immunity.

The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of CTNNB1 gene expression and/or activity, and/or modulate a beta-catenin gene expression pathway. Specifically, the invention relates to double-stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules that are capable of mediating or that mediate RNA interference (RNAi) against CTNNB1 gene expression.

The present disclosure provides polynucleotide guides for use in CRISPR-Cas systems wherein such polynucleotides contain at least one CRISPR abasic restricted nucleotide (CABRNT) and/or at least one CRISPR accuracy via analogs (CAVA) nucleotide. CRISPR guides that contain at least one abasic site and/or at least one base analog, as well as nucleoprotein complexes of CRISPR-Cas proteins and CABRNT, CAVA, and CABRNT-CAVA guides are also described. Also disclosed are methods for making and using the CABRNT, CAVA, and CABRNT-CAVA polynucleotides and guides and the CABRNT/Cas, CAVA/Cas, and CABRNT-CAVA/Cas nucleoprotein complexes of the present invention.

Provided are a glypican-3 (GPC3)-specific modified aptamer, and prevention or treatment of hepatoma using the same. The glypican-3-specific modified aptamer of the present invention specifically binds to glypican-3 to be internalized into hepatoma cells, and exhibits anticancer activity through an anticancer agent bound to the aptamer, and therefore, has a selective anticancer effect only for GPC3-expressing hepatoma cells without affecting normal hepatocytes.

The invention provides compositions and methods for reducing expression of a target gene in a cell, involving contacting a cell with an isolated double stranded nucleic acid (dsNA) in an amount effective to reduce expression of a target gene in a cell. The dsNAs of the invention possess a single stranded extension (in most embodiments, the single stranded extension comprises at least one modified nucleotide and/or phosphate back bone modification). Such single stranded extended Dicer-substrate siRNAs (DsiRNAs) were demonstrated to be effective RNA inhibitory agents compared to corresponding double stranded DsiRNAs.

The invention provides compositions and methods for reducing expression of a target gene in a cell, involving contacting a cell with an isolated double stranded nucleic acid (dsNA) in an amount effective to reduce expression of a target gene in a cell. The dsNAs of the invention possess a single stranded extension (in most embodiments, the single stranded extension comprises at least one modified nucleotide and/or phosphate back bone modification). Such single stranded extended Dicer-substrate siRNAs (DsiRNAs) were demonstrated to be effective RNA inhibitory agents compared to corresponding double stranded DsiRNAs.

Disclosed herein are compositions and pharmaceutical formulations that comprise a binding moiety conjugated to a polynucleic acid molecule and a polymer. Also described herein include methods for treating a cancer which utilize a composition or a pharmaceutical formulation comprising a binding moiety conjugated to a polynucleic acid molecule and a polymer.