Compounds, compositions and methods are provided for modulating the expression and function of small non-coding RNAs. The compositions comprise oligomeric compounds, targeted to small non-coding RNAs. Methods of using these compounds for modulation of small non-coding RNAs as well as downstream targets of these RNAs and for diagnosis and treatment of disease associated with small non-coding RNAs are also provided.

The invention relates to RNAi agents, e.g., double-stranded RNAi agents, targeting the PCSK9 gene, and methods of using such RNAi agents to inhibit expression of PCSK9 and methods of treating subjects having a lipid disorder, such as a hyperlipidemia.

The invention relates to a RNA interference triggers for inhibiting the expression of an AAT gene through the mechanism of RNA interference. The invention also relates to a pharmaceutical composition comprising the AAT RNAi trigger together with an excipient capable of improving delivery of the RNAi trigger to a liver cell in vivo. Delivery of the AAT RNAi trigger to liver cells in vivo provides for inhibition of AAT gene expression and treatment of alpha 1-antitrypsin deficiency and associated diseases.

The present invention provides an aptamer that binds to IL-21, an aptamer that binds to IL-21 and inhibits the binding of IL-21 and a receptor thereof, and an aptamer that binds to IL-21 and contains a nucleotide sequence represented by the formula (1): CGRYKACY wherein R is A or G, Y is C or U, and K is G or U.

The disclosure relates, in some aspects, to methods and compositions for production of immunomodulatory compositions. In some embodiments, the disclosure provides host cells which have been treated ex vivo with one or more oligonucleotide agents capable of controlling and/or reducing the differentiation of the host cell. In some embodiments, compositions and methods described by the disclosure are useful as immunogenic modulators for treating cancer.

A preparation method and application of a single emulsifier and a double emulsion based on DNA triangular origami technology include designing and synthesizing staple strands of DNA triangular origami; mixing DNA scaffold strand and staple strands to synthesize the DNA triangular origami; purifying and enriching the triangular origami; and preparing the double emulsion. A process of the disclosure is simple, the obtained DNA triangular origami can be used as a single emulsifier of the double emulsion, the prepared emulsion can deliver hydrophilic arbutin and hydrophobic coumaric acid at the same time, and a central nano hole of the DNA triangular origami can be used as a nano channel for releasing arbutin and coumaric acid. Zero-order release can be achieved through an intermolecular force between arbutin and coumaric acid and the DNA triangular origami and pore confinement effect.

The present invention provides compositions and methods for treating cancer with peptide nucleic acid agents. In some embodiments, the present invention provides methods and compositions relating to peptide nucleic acid agents that target oncogenes. For example, the present invention provides compositions, including pharmaceutical compositions, comprising agents specific for BRAF V600E inhibition, or fragments or characteristic portions thereof. The present invention further provides various therapeutic and/or diagnostic methods of using BRAF V600E specific peptide nucleic acid agents and/or compositions.

In some embodiments, the invention is directed to a method for diagnosing fibrosis and/or fibrosis related diseases and to a method for screening a pharmaceutically active compound for the treatment of fibrosis and/or fibrosis related diseases. The present invention further relates to compositions for use in the treatment, amelioration, and/or prevention of fibrosis. In certain embodiments, the compositions modulate the activity of a miRNA for the treatment, amelioration, and/or prevention of fibrosis. In certain embodiments, the compositions inhibit the activity of miR-21 for the treatment, amelioration, and/or prevention of fibrosis.

The present invention relates, in general to agents that modulate the pharmacological activity of siRNAs. In addition, the invention relates generally to methods and systems for use in assessing the efficacy and safety of a pharmaceutical composition for use in the treatment or prophylaxis of a disease.

This disclosure relates to novel SARS-CoV-2 targeting sequences. Novel SARS-CoV-2 targeting oligonucleotides for the treatment of SARS-CoV-2 infection are also provided.