Abstract: Provided herein are compositions comprising EV, e.g., exosome, which comprises STING agonists and methods of using such compositions for the treatment of neuroimmunological disorders. Methods of producing the compositions (e.g., EVs comprising a STING agonist) described herein are also provided.

Provided herein are immunomodulatory proteins that exhibit neutralizing activity of BAFF and APRIL (or BAFF/APRIL heterotrimers) alone, or also coupled with inhibition of T cell costimulation. The immunomodulatory proteins provided herein include variant domains of B cell maturation antigen (BCMA) alone, or multi-domain immunomodulatory protein that inhibit B cell responses and also can inhibit T cell costimulation. Also provided are nucleic acids molecules encoding the immunomodulatory proteins. The immunomodulatory proteins provide therapeutic utility for a variety of immunological diseases or conditions. Also provided are compositions and methods for making and using such proteins.

The technology described herein is directed to polypeptide systems using drug-controlled peptide docking domains and cognate docking domain-binding peptides and their use to control cellular signaling, activity, and/or gene expression.

Provided herein are nucleic acids for expressing modified ligand-gated ion channel proteins in excitable cells or secretory cells, such as nerves and neurons and optionally including viral sequences, such as Adeno-associated virus sequences, for delivery to excitable cells or secretory cells of a patient. Also provided herein are methods of modulating cell membrane potentials in an excitable cell or secretory cell, and for treatment of a disease or disorder associated with the nervous system in a patient, such as chronic pain or itch.

Provided are bifunctional molecules that include a first moiety that specifically binds a cell surface molecule or extracellular molecule, and a second moiety that specifically binds a lysosomal targeting molecule. The bifunctional molecules find use, e.g., for targeted degradation of cell surface and extracellular molecules (e.g., proteins) via the endosomal/lysosomal pathway. Also provided are compositions and kits that include the bifunctional molecules, as well as methods of using the bifunctional molecules. Methods of making bifunctional molecules are also provided.

An environmentally sensitive membrane binding polypeptide, pH (low)-sensitive membrane peptide (pHLIP) has improved insertion kinetics balanced with solubility to selectively target acidic tissues.

Provided herein are immunomodulatory proteins that exhibit neutralizing activity of BAFF and APRIL (or BAFF/APRIL heterotrimers). The immunomodulatory proteins provided herein include variant domains of Transmembrane Activator and CAML Interactor (TACI). Among provided immunodulatory proteins are TACI-Fc fusion proteins. Also provided are nucleic acid molecules encoding the immunomodulatory proteins. The immunomodulatory proteins provide therapeutic utility for a variety of immunological diseases, disorders or conditions. Also provided are compositions and methods for making and using such proteins.

The invention provides a nanoparticle comprising: a core comprising a metal and/or a semiconductor; and a plurality of ligands covalently linked to the core, wherein said ligands comprise: at least one liver-targeting ligand; at least one payload ligand comprising a bioactive agent; and at least one dilution ligand comprising a carbohydrate. Also provided are pharmaceutical compositions comprising the nanoparticles, medical uses thereof, including in the treatment and imaging of liver cancers, and processes for the production of the nanoparticles.

Provided are ciliary neurotrophic factor receptor (CNTFR) ligands. In certain aspects, a CNTFR ligand of the present disclosure exhibits increased affinity for CNTFR relative to the corresponding wild-type CNTFR ligand. In certain aspects, a CNTFR ligand of the present disclosure results in reduced binding affinity of glycoprotein 130 (gp130), leukemia inhibitory factor receptor (LIFR), or both, for a complex including the CNTFR ligand and CNTFR, relative to the binding affinity for a complex including the corresponding wild-type CNTFR ligand and CNTFR. In certain aspects, a CNTFR ligand of the present disclosure has both of the aforementioned properties. Also provided are pharmaceutical compositions including the CNTFR ligands, as well as methods of using the CNTFR ligands.

The present embodiments provide compounds and methods for targeting cells expressing GLP-1 receptor.