Provided herein are oligomeric compounds with conjugate groups. In certain embodiments, the oligomeric compounds are conjugated to N-Acetylgalactosamine.

Provided herein are cell penetrating conjugates. The conjugates include a non-cell penetrating protein attached to a phosphorothioate nucleic acid or phosphorothioate polymer backbone through a non-covalent linker including abiotin-binding domain and a biotin domain, wherein the phosphorothioate nucleic acid or phosphorothioate polymer backbone enhances intracellular delivery of the non-cell penetrating protein. Also provided are compositions and kits comprising the conjugates.

Provided herein are micellic assemblies comprising a plurality of copolymers. In certain instauces, micellic assemblies provided herein are pH sensitive particles.

Disclosed are compounds and compositions for the activation or induction of expression of a pattern recognition receptor (e.g., STING, RIG-I, MDA5), and methods of use thereof.

The present invention provides a mannose-based mRNA targeted delivery system and use thereof. The mRNA can encode one or more target polypeptides and contains at least one mannose modification. The technical solution of the present invention modifies the mRNA molecule with a mannose, so that the mRNA can be directly and efficiently coupled with the mannose, and the targeted delivery of the mRNA is realized without the need for a carrier.

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 disclosure features methods for treating solid tumor malignancies and lymphomas by administering LNP encapsulated mRNAs encoding human OX40L, IL-23 and IL-36γ polypeptides alone or in combination with checkpoint blockade. The disclosure also features compositions for use in the methods.

This application relates to potent oligonucleotides useful for reducing HBsAg expression and treating HBV infections.

The present invention relates to oligonucleotide conjugates and preparation and applications thereof. In particular, the present invention relates to an oligonucleotide conjugated to a biomolecule (e.g. an antibody) and/or an agent of interest (e.g. a drug). In certain embodiments, the oligonucleotide of the present invention is a hybridized complex of a single strand oligonucleotide carrying a biomolecule and a complementary strand oligonucleotide bearing an agent of interest where the hybridized nucleotide segment acts as a linker to link the biomolecule and the agent of interest in one molecule.

Aspects of the disclosure relate to complexes comprising a muscle-targeting agent covalently linked to a molecular payload. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on muscle cells. In some embodiments, the molecular payload promotes the expression or activity of a functional dystrophin protein. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide, e.g., an oligonucleotide that causes exon skipping in a mRNA expressed from a mutant DMD allele.