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

Described herein are RNA-based antisense therapeutics to target antibiotic resistant bacteria. The antisense therapeutics disclosed herein can be useful in re-sensitizing drug-resistant bacteria to antibiotics, as well as developing antibiotics that have bactericidal or bacteriostatic effects on the drug-resistant bacteria or are capable of preventing emergence of antibiotic resistance. Also described herein are methods for re-sensitizing a subject to one or more antibiotics in need thereof, methods for identifying target genes involved in adaptive antibiotic resistance in bacteria, and methods for developing antibacterial antisense therapeutics.

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.

Disclosed herein are compositions and pharmaceutical formulations that comprise a binding moiety conjugated to a modified 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.

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.

Peptide-based systems containing hydrophobic amino acids (e.g., tryptophan), charged amino acids (e.g., arginine), and/or sulfur-containing amino acids (e.g., cysteine), which can be used either alone or in combination with nanoparticles (e.g., gold or silver nanoparticles) for siRNA delivery into living cells are disclosed.

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.

The invention relates to peptide linkers and fusion proteins comprising linkers designed for optimizing the activity of the proteins comprised therein, and methods for using the same. The invention further relates to newly designed Cas12a-based cytosine base editors.

Disclosed herein are polynucleic acid molecules, pharmaceutical compositions, and methods for treating muscle dystrophy (DM1).

Disclosed herein are compounds according to Formula (I) comprising PK/PD modulators for delivery of oligonucleotide-based agents, e.g., double stranded RNAi agents, to certain cell types, such for example skeletal muscle cells, in vivo. The PK/PD modulators disclosed herein, when conjugated to an oligonucleotide-based therapeutic or diagnostic agent, such as an RNAi agent, can enhance the delivery of the composition to the specified cells being targeted to facilitate the inhibition of gene expression in those cells.

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