The invention provides, inter alia, conjugates comprising a coagulating agent conjugated to an antibody, where the antibody specifically binds an extracellular domain epitope of a mammalian PLVAP protein. These agents specifically target HCC tumors and treat the HCC. The invention also provides methods of using these conjugates, such as methods of treating HCC by administering the conjugates provided by the invention or compositions provided by the invention, such as pharmaceutical compositions.

A novel recombinant antimicrobial multidomain polypeptide in an aggregated and functional format is provided. The antimicrobial multidomain polypeptide comprises at least three peptidic domains: a) a non-enzymatic antimicrobial peptidic domain from mammal's immune system, b) a bacterial binding peptidic domain which interacts with the bacterial cell wall or membrane, and c) an enzymatic antimicrobial peptidic domain from mammal's immune system. The antimicrobial multidomain polypeptide exhibits a broad-spectrum antimicrobial effect and is produced in an efficient production system, i.e in form of inclusion bodies.

Provided are conjugates including a targeting moiety that binds to a cell surface molecule of a target cell and a target cell surface-editing enzyme. Also provided are compositions and kits that include the conjugates, as well as methods of using the conjugates. Methods of making conjugates are also provided.

Non-human animal genomes, non-human animal cells, and non-human animals comprising a humanized TRKB locus and methods of making and using such non-human animal genomes, non-human animal cells, and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized TRKB locus express a human TRKB protein or a chimeric transthyretin protein, fragments of which are from human TRKB. Methods are provided for using such non-human animals comprising a humanized TRKB locus to assess in vivo efficacy of human-TRKB-targeting reagents such as nuclease agents designed to target human TRKB.

The present application relates to compositions for preventing or treating viral and other microbial infections. In some embodiments, the present application provides chimeric proteins comprising a target-binding moiety that specifically binds to a pathogen that infects through a mucosa, and a positively charged mucoadhesive peptide fragment. Also provided are antibodies and constructs thereof that specifically binds to an S1 subunit of a spike protein of SARS-CoV-2. Compositions comprising the chimeric proteins, antibodies, or constructs described herein are useful for preventing or treating a microbial infection in an individual, such as a coronavirus infection.

Herein a Bacillus exosporium antigen delivery (BEAD) system that provides a means to introduce recombinant proteins or small molecules into the exosporium of members of the B. cereus family of bacteria, i.e. B. anthracis, B. cereus, and B. thuringiensis, is disclosed. The system results in the surface display of recombinant proteins or small molecules such that they can stimulate an immune response. In addition, methods of making and using the system are described.

Described herein is the discovery of novel PSMA-specific peptides, which were identified through a novel combinatorial biopanning method. One of the novel PSMA-specific peptides discovered, GTIQPYPFSWGY (or GTI) (SEQ ID NO: 2), exhibits high binding affinity and selectivity to PSMA and PSMA-positive prostate cancer cells. It was found that GTI can mediate internalization of the apoptotic KLA peptide to PSMA-positive LNCaP cells and induce cell death. Moreover, a FAM-labeled GTI peptide shows a high and specific tumor uptake in nude mice bearing human prostate cancer xenografts. It was demonstrated that the GTI peptide can be employed as a PSMA-specific ligand for prostate cancer diagnosis and/or for targeted drug delivery to prostate cancer cells.

The invention features multi-specific protein complexes with one domain comprising IL-15 or a functional variant and a binding domain specific to a disease antigen, immune checkpoint or signaling molecule.

This disclosure provides methods and compositions for treating TTP based on transfusion of a relatively small number of genetically modified red blood cells. The genetically modified red blood cells express a fusion protein including a fragment of ADAMTS13 that is enzymatically active against von Willebrand factor (VWF). The fragments of ADAMTS13 can be resistant to the inhibitors, e.g., the auto-immune antibodies, which are responsible for the acquired form of TTP.

Genetically modified cells that are compatible with multiple subjects, e.g., universal donor cells, and methods of generating said genetic modified cells are provided herein. The universal donor cells comprise at least one genetic modification within or near a gene that encodes one or more MHC-I or MHC-II human leukocyte antigens or a component or a transcriptional regulator of a MHC-I or MHC-II complex, wherein genetic modification comprises an insertion of a polynucleotide encoding a tolerogenic factor and/or survival factor. The universal donor cells may further comprise at least one genetic modification within or near a gene that encodes a survival factor, wherein said genetic modification comprises an insertion of a polynucleotide encoding a second tolerogenic factor and/or a different survival factor.