Disclosed are compositions comprising a nucleic acid sequence conjugated to one or more MGS peptides. Disclosed are methods of modifying gene expression of a gene of interest comprising administering to a cell a composition comprising a nucleic acid sequence conjugated to one or more MGS peptides, wherein the nucleic acid sequence binds to the RNA transcribed from the gene of interest, the gene of interest or a sequence upstream of the gene of interest. Disclosed are methods of targeting a gene of interest in an intracellular target comprising administering to a cell a composition comprising a nucleic acid sequence conjugated to one or more MGS peptides, wherein the MGS peptide targets the intracellular target, wherein the nucleic acid sequence binds to the RNA transcribed from the gene interest in an intracellular target.

The present disclosure provides for antibody-oligonucleotide conjugates, methods of preparation thereof, and methods of use thereof. Also provided are related compounds, compositions and kits.

The invention relates to carrier complexes and methods for delivering molecules to cells. The carrier complexes comprises a molecule and an aromatic cationic peptide in accordance with the invention. In one embodiment, the method for delivering a molecule to a cell comprises contacting the cell with a carrier complex. In another embodiment, the method for delivering a molecule to a cell comprises contacting the cell with a molecule and an aromatic cationic peptide.

The present disclosure relates to compositions, such as siRNA molecules and FN3 domains conjugated to the same, as well as methods of making and using the molecules.

Antisense molecules capable of binding to a selected target site in the human dystrophin gene to induce exon 53 skipping are described.

The present disclosure relates to modified antisense oligonucleotides. The nucleotides described herein are of 10 to 40 nucleobases and include a targeting sequence complementary to a target region within intron 1 of a pre-mRNA of the human alpha glucosidase (GAA) gene. The target region includes at least one additional nucleobase compared to the targeting sequence, wherein the at least one additional nucleobase has no complementary nucleobase in the targeting sequence, and wherein the at least one additional nucleobase is internal to the target region.

Antisense oligomers complementary to a selected target site in the human dystrophin gene to induce exon 2 skipping are described. In various aspects, antisense oligomers are described according to Formula (I): Formula (I) or a pharmaceutically acceptable salt thereof, wherein T, Nu, n, and R.sup.100 are defined herein.

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The present disclosure relates to nucleic acid-peptide-nucleic acid conjugate molecules and to methods for synthesizing nucleic acid-peptide-nucleic acid conjugate molecules. In some embodiments, a method for synthesizing a nucleic acid-peptide-nucleic acid conjugate molecule using proximity-enhanced synthesis includes covalently linking a peptide with a first nucleic acid strand via a first reaction, hybridizing the first nucleic acid strand with a second nucleic acid strand to bring the second nucleic acid strand in proximity to the peptide, and covalently linking the peptide with the second nucleic acid strand via a second reaction to provide the nucleic acid-peptide-nucleic acid conjugate molecule. In some embodiments, the peptide of the nucleic acid-peptide-nucleic acid conjugate molecule is a substrate for cleavage by an enzyme, such as matrix metalloproteinase-8 (MMP-8). Exemplary applications of the nucleic acid-peptide-nucleic acid conjugate molecule for drug delivery, molecular assembly of hybrid structures, and constraining the peptide to a biologically active conformation are also disclosed.

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 inhibits expression or activity of DUX4. In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.

Methods and compositions related to type 2 diabetes therapy are described, where the methods and compositions relieve ER stress in pancreatic islet cells. The present disclosure provides methods and compositions for reducing hepatic steatosis, e.g., associated with Type 2 diabetes (T2D). In one aspect, the present disclosure provides a method of reducing hepatic steatosis, e.g., associated with T2D, in a subject in need thereof.