The present invention includes compositions and methods of making and using a fusion protein comprising a peptide, a first flexible linker, a β2-microglobulin domain, a second flexible linker, a soluble major histocompatibility complex (MHC) heavy chain and a peptide tag.

The present invention is directed generally to cell-targeted cytotoxic constructs comprising a targeting polypeptide, a linking polypeptide and a cytotoxic polypeptide. Preferably, (a) the targeting polypeptide is a R-spondin1 (RSPO1), R-spondin2 (RSPO2) or yoked chorionic gonadotropin (YCG), the linking polypeptide comprises LPXT (SEQ ID NO: 56) or NPXT (SEQ ID NO: 60) as well as others, where X is any amino acid, the linking polypeptide being positioned between the targeting ligand and (c) the cytotoxic moiety is an auristatin or a truncated serine protease, the serine protease having an IIGG (SEQ ID NO: 91), IVGG (SEQ ID NO: 92) or ILGG (SEQ ID NO: 93) at its N-terminus. Such constructs can be used in methods for targeted cell killing such as for treatment cell of proliferative diseases (e.g., cancer).

The present disclosure provides compositions and methods for treating or preventing ulcers in subjects having low red blood cell levels and/or hemoglobin levels (e.g, anemia). In some embodiments, the compositions of the disclosure may be used to treat or prevent ulcers associated with anemia.

The present invention relates to a method for preparing a labelled polypeptide, the method comprising: a. providing a polypeptide comprising: i. a sortase acceptor site or a sortase donor site; ii. a non-cytotoxic protease or a proteolytically inactive mutant thereof; iii. a Targeting Moiety (TM) that is capable of binding to a Binding Site on a target cell; and iv. a translocation domain; b. incubating the polypeptide with: a sortase; and a labelled substrate comprising a sortase donor site or a sortase acceptor site, respectively, and a conjugated detectable label; wherein the sortase catalyses: conjugation between an amino acid of the sortase acceptor site of the polypeptide and an amino acid of the sortase donor site of the labelled substrate; or conjugation between an amino acid of the sortase acceptor site of the labelled substrate and an amino acid of the sortase donor site of the polypeptide; thereby labelling the polypeptide; and c. obtaining the labelled polypeptide. The invention also relates to polypeptides for labelling, labelled polypeptides, nucleic acids encoding said polypeptides, and methods of using and manufacturing said polypeptides.

The present disclosure provides T-cell modulatory multimeric polypeptide epitope conjugates comprising an immunomodulatory polypeptide (“MOD”) that may be selected to exhibit reduced binding affinity to a cognate co-immunomodulatory polypeptide (“Co-MOD”) and a conjugated Wilms tumor-1 (WT-1) epitope presenting peptide. The T-Cell-MMP-epitope conjugates are useful for modulating the activity of a T-cell by delivering immunomodulatory peptides, such as IL-2 or IL-2 variants that exhibit reduced binding affinity for IL-2R, to the T-cells in a WT-1 epitope selective/specific manner, and accordingly, for treating individuals, particularly those with acute myeloid leukemia, myeloma, ovarian cancer, pancreatic cancer, non-small cell lung cancer, colorectal cancer, breast cancer, Wilms tumor, mesothelioma, soft tissue sarcoma, neuroblastoma, or nephroblastoma.

Methods and compositions related to intracellular delivery of gene editing proteins are provided. The invention relates to compositions and methods for transporting gene editing polypeptides, such as Cas9 or Cas12, into a cell ex vivo or in vivo. The invention includes a targeted active gene editing (TAGE) agent that includes an extracellular cell membrane binding moiety, e.g., an antigen binding polypeptide, a cell penetrating peptide (CPP), a ligand, or combinations thereof, that specifically binds to an extracellular cell membrane-bound molecule (e.g., a cell surface molecule), and a site-directed modifying polypeptide that recognizes a nucleic acid sequence. The extracellular cell membrane binding moiety (e.g., antigen binding polypeptide, CPP, or ligand) and the site-directed modifying polypeptide are stably associated such that the site-directed modifying polypeptide can be internalized into a cell, such as one displaying an extracellular cell membrane-bound molecule recognized by the extracellular cell membrane binding moiety.

Provided by the present invention are a novel GLP-1 fusion protein and a conjugate thereof, a pharmaceutical composition containing same, and a use thereof in reducing blood sugar or body weight, especially for treating diabetes, in particular type II diabetes.

Provided herein are, inter alia, compositions and methods for demethylating and methylating a target DNA sequences in a mammalian cell. The compositions and methods are, useful for activity modulation of a targeted gene, or to create a gene regulatory network.

The present invention relates to an immunogenic polypeptide, a nucleic acid encoding the same, a pharmaceutical composition comprising the same and the immunogenic polypeptide, nucleic acid or pharmaceutical composition for use as a medicament, particularly a vaccine, or for use in a method of treating or preventing a Borrelia infection.

Provided are recombinant fusion proteins comprising an interleukin-18-binding protein and an antigen binding fragment against serum albumin and uses thereof. The recombinant fusion proteins have an improved administration cycle due to an increase in the half-life in the body. Further, the recombinant fusion proteins have low immunogenicity and do not cause side effects in vivo, and therefore, can be effectively used for the treatment of various cancers and immune diseases and conditions.