The present invention relates to binding fusion protein compositions comprising targeting moieties linked to extended recombinant polypeptide (XTEN), binding fusion protein-drug conjugate compositions, and XTEN-drug conjugate compositions, isolated nucleic acids encoding the compositions and vectors and host cells containing the same, and methods of using such compositions in treatment of diseases, disorders, and conditions.

Embodiments provided herein include methods and compositions comprising anti-dinitrophenol chimeric antigen receptors (CARs). Some embodiments include nucleic acids encoding such CARs, polypeptides encoded by such nucleic acids, cells comprising such nucleic acids or polypeptides, and methods utilizing such cells. Some embodiments also include the use of dinitrophenol (DNP) and derivatives thereof.

Provided herein are cytokines or functional fragments thereof that, in some embodiments, are engineered to be masked by a masking moiety at one or more receptor binding site(s) of the cytokine or functional fragment thereof. In some embodiments, the cytokines are engineered to be activatable by a protease at a target site, such as in a tumor microenvironment, by including a proteolytically cleavable linker. In some embodiments, the proteolytically cleavable linker links the cytokine to the masking moiety, links the cytokine to a half-life extension domain, and/or links the masking moiety to a half-life extension domain. The masking moiety blocks, occludes, inhibits (e.g., decreases) or otherwise prevents (e.g., masks) the activity or binding of the cytokine to its cognate receptor or protein. Upon proteolytic cleavage of the cleavable linker at the target site, the cytokine becomes activated, which renders it capable of binding to its cognate receptor or protein with increased affinity.

The present invention relates to a cellular transport system for bringing a sulfonic acid construct which carries a cargo into a cell and releasing the cargo in the cell's cytoplasm, the cellular transport system comprising: (i) a sulfonate transporter located in the cytoplasm membrane of the cell wherein said sulfonate transporter is capable of transporting said sulfonic acid construct across the cytoplasm membrane into the cytoplasm; (ii) a γ-glutamyl transferase (GGT; EC 2.3.2.2) which is modified to be located in the cytoplasm of the cell, wherein said γ-glutamyl transferase is capable of hydrolyzing said sulfonic acid construct so as to release the cargo. Moreover, the present invention relates to the use of a cellular transport system for bringing a sulfonic acid construct which contains a cargo into a cell and releasing the cargo in the cell's cytoplasm. Further, the present invention relates to a γ-glutamyl transferase for hydrolyzing a sulfonic acid construct which contains a cargo.

A protein transduction domain and a fusion compound, which are more efficient, are proposed. As a result of selecting and testing a number of candidate peptides, the present inventors found that a GK1 peptide comprising 18 amino acids and a modified sequence obtained by replacing, adding, or deleting some sequences are bonded to high-molecular-weight materials such as proteins based on the basic sequence of the peptide, thus enabling the high-molecular-weight materials to smoothly penetrate into living bodies, for example, cells, tissues, or blood. A fusion compound, oligonucleotide, or vector using the same may be applied as a pharmaceutical composition for preventing or treating diseases.

Glycotargeting therapeutics are useful in the treatment of transplant rejection, autoimmune disease, food allergy, and immune response against a therapeutic agent.

The present disclosure provides engineered SARS-CoV-2 spike ectodomain polypeptides and cells for producing such a polypeptide, as well as compositions and methods thereof.

Several embodiments of the present disclosure relate to glycotargeting therapeutics that are useful in the treatment of transplant rejection, autoimmune disease, food allergy, and immune response against a therapeutic agent. In several embodiments, the compositions are configured to target the liver and deliver antigens to which tolerance is desired. Methods and uses of the compositions for induction of immune tolerance are also disclosed herein.

The present disclosure relates to extracellular vesicles (EVs) that are capable of targeting a cell in the CNS of a subject. Also provided herein are methods for producing the EVs and methods for using the EVs to treat and/or prevent diseases or disorders of the CNS (e.g., neurological disorders).

Aspects of the disclosure relate to molecular payloads that modulate the expression or activity of genes involved in muscle growth and maintenance (e.g., MSTN, INHBA, and/or ACVR1B), and complexes comprising a muscle-targeting agent covalently linked to such molecular payloads. In some embodiments, the muscle-targeting agent specifically binds to an internalizing cell surface receptor on a muscle cell (e.g., a cardiac muscle cell). In some embodiments, the molecular payload is an oligonucleotide, such as an antisense oligonucleotide or RNAi oligonucleotide.