The present disclosure relates to methods for improving myogenic differentiation capacity of a cell line or an immortalized cell line. For example, the present disclosure relates to methods of exposing an immortalized cell line (e.g., an immortalized fibroblast cell line) to culture media comprising signaling pathway agonists, antagonist, or a combination thereof in order to improve differentiation capacity. In another example, the present disclosure relates to methods of improving differentiation capacity of a cell line or an immortalized cell line where the method includes transforming an immortalized cell line with one or more myogenic regulatory factors and exposing the immortalized cell line to culture media comprising signaling pathway agonists, antagonists, or a combination thereof.

The invention is in the field of therapy of gut inflammatory diseases such as Inflammatory Bowel Diseases (IBD) or Irritable Bowel Syndrome (IBS) including Gluten hypersensitivity. The inventors showed that ELA2A secreted by epithelial cells in the extracellular space is over-expressed in IBD conditions degrading tight junction proteins and controlling cytokines expression. Overexpression of ELA2A conferred a pro-inflammatory phenotype both in cell expression systems and in vivo in animal model of IBD. The inventors also showed that ELA2 over-expressing intestinal epithelial cells increase the release of CXCL8 protein compared to control cells. The increased CXCL-8 protein release observed in cells overexpressing ELA2A is inhibited by ELAFIN addition to the culture, in a dose-dependent manner. In particular, the invention relates to inhibitors of Elastase ELA2A, for use in the treatment of Inflammatory Bowel Diseases, such as Crohn's Disease, Ulcerative Colitis, Celiac disease, and Pouchitis.

The present disclosure relates to therapeutic use of anti-EpCAM antibodies. Also provided is a combination immune therapy of an anti-EpCAM antibody and a PD-L1 immune checkpoint inhibitor.

Some aspects of this disclosure provide compositions, methods, systems, and kits for controlling the activity and/or improving the specificity of RNA-programmable endonucleases, such as Cas9. For example, provided are guide RNAs (gRNAs) that are engineered to exist in an “on” or “off” state, which control the binding and hence cleavage activity of RNA-programmable endonucleases. Some aspects of this disclosure provide mRNA-sensing gRNAs that modulate the activity of RNA-programmable endonucleases based on the presence or absence of a target mRNA. Some aspects of this disclosure provide gRNAs that modulate the activity of an RNA-programmable endonuclease based on the presence or absence of an extended DNA (xDNA).

Disclosed herein, in certain embodiments, are recombinant Arc and endogenous Gag polypeptides, and methods of using recombinant Arc and endogenous Gag polypeptides.

The present disclosure relates to an inhibitor of Dynamin 2 for use in the treatment of centronuclear myopathies. The present disclosure relates to pharmaceutical compositions containing Dynamin 2 inhibitor and to their use for the treatment of centronuclear myopathies. It also deals with a method for identifying or screening molecules useful in the treatment of a centronuclear myopathy.

Disclosed herein are glutathione-sensitive oligonucleotides and methods of using the same. Any oligonucleotide of interest may be modified with a glutathione-sensitive moiety, including oligonucleotides used for in vivo delivery, such as nucleic acid inhibitor molecules. Typically, the glutathione-sensitive moiety is used to reversibly modify the 2′-carbon of a sugar moiety in one or more nucleotides in the oligonucleotide, although other carbon positions may also be modified with the glutathione-sensitive moiety. Also disclosed are glutathione-sensitive nucleotide and nucleoside monomers, including glutathione-sensitive nucleoside phosphoramidites that can be used, for example, in standard oligonucleotide synthesis methods. In addition, glutathione-sensitive nucleotide and nucleoside monomers without a phosphoramidite can be used therapeutically, for example, as anti-viral agents.

A transfection reagent composition comprising: 30-60 MOL. % of a cationic lipid, or a pharmaceutical acceptable salt thereof; 10-60 MOL % of a structural lipid; 10-20 MOL % of a triglyceride; and 0.1 to about 10 MOL. % of a stabilizing agent, is provided. The transfection agent is effective in transfecting cells, particularly neurons, with siRNA, mRNA and plasmid nucleic acid, Sand maintaining viability of the cells as well as activity of the delivered nucleic acid.

Provided herein are methods of treating a subject that include administering a therapeutically effective amount of an NLPR3 antagonist or a pharmaceutically acceptable salt, solvate, or co-crystal thereof to a subject identified as having a cell that has an elevated level of NLRP3 inflammasome activity and/or expression as compared to a reference level. Provided herein are methods of treating a subject, methods of selecting a treatment for a subject, methods of selecting a subject for treatment, and methods of selecting a subject for participation in a clinical study that include the administration of a therapeutically effective amount of an NLRP3 antagonist. Also provided are methods of treating a subject having resistance to an anti-TNFα agent and methods of determining the efficacy of treatment with an anti-TNFα agent. Also provided are methods of treating a subject with a combination of an NLRP3 antagonist and an anti-TNFα agent.

The present disclosure provides methods comprising administering to the individual an effective amount of an agent that decreases or inhibits TIGIT expression and/or activity and an anti-cancer agent and/or an anti-cancer therapy. Further provided are kits comprising an anti-cancer agent, an agent that decreases or inhibits TIGIT expression and/or activity, or both, as well as instructions for use thereof.