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.

The disclosure provides fusion reporter protein constructs and related compositions, systems, and methods for nanopore-based detection biological activity. In one aspect, the disclosure provides a fusion reporter protein comprising, in order: a blocking domain with a stably folded tertiary structure; a flexible analyte domain; and a flexible tail domain, wherein the flexible tail domain has a net negative charge. The disclosure also provides nucleic acid constructs encoding the disclosed fusion reporter protein, and vectors and cells comprising the nucleic acids. Also provided are nanopore-based systems and methods for using the disclosed fusion reporter protein constructs to detect and characterize biological activity.

The present disclosure provides compositions and methods for sensing a target substance of interest in the environment and inducing gene expression in response thereto, useful for detection of biological and chemical agents and environmental pollutants.

Described herein are compositions and techniques related to generation and therapeutic application of artificial synapses. Artificial synapses are engineered extracellular vesicles, including exosomes, which incorporate sticky binders on their surface to anchor signaling domains against biological targets, such as receptors. These engineered additives can be organized in genetic vector constructs, expressed in mammalian cells, wherein the sticky binders attach to extracellular vesicles such as exosomes, thereby presenting their joined signaling domains which are rapidly taken up by recipient cells. Artificial synapses adopt the hallmark biophysical and biochemical features of extracellular vesicles, allowing for rapid deployment and scale-up. Importantly, this strategy can allow for kinetically favorable signal generation and signal propagation. This includes, for example, increasing density of agonist presentation to support receptor clustering—an onerous barrier for traditional receptor targeting strategies.

Embodiments of the invention are generally directed to lignin-modifying enzymes and systems and methods of their manufacture. In many embodiments, yeast strains, including S. cerevisiae, are used to produce and secrete lignin-modifying enzymes Further embodiments are directed to methods to screening peroxidase-producing yeast strains, including S. cerevisiae. Additional embodiments are directed to an expression vector or cassette encoding for a protein of interest and one or more proteins to allow for surface to display of the protein of interest.

Provided is a vector capable of co-expressing two different target proteins on the microbial surface using two promoters derived from Lactobacillus, and a method of expressing target proteins on the microbial surface using the vector. The vector containing foreign genes inserted therein is transformed into a microorganism, and allows different foreign proteins to be stably expressed on the surface of the microorganism. Furthermore, provided is a surface expression vector containing the gene pgsA encoding a poly-gamma-glutamate synthetase complex, and a method of expressing a target protein on the microbial surface using the vector. The vector containing foreign genes inserted therein is transformed into a microorganism, and allows the foreign proteins to be stably expressed on the surface of the microorganism.

Described herein are immune cells comprising: a T-cell receptor (TCR) and a chimeric stimulating receptor (CSR) that comprises (i) a ligand-binding module that is capable of binding or interacting with a target ligand; (ii) a transmembrane domain; and (iii) a CD30 costimulatory domain, in which the CSR in the immune cells lacks a functional primary signaling domain. Also provided herein are methods of using the same or components thereof (e.g., the CSR) for therapeutic treatment of cancers (e.g., solid tumor cancers).

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.

The present disclosure relates in some aspects to methods and compositions for analyzing a biomolecule, such as an antibody, and/or analyzing a repertoire comprising biomolecules, such as the repertoire of antibody binding specificities in a sample comprising one or more antibodies. Exemplary samples include serum and plasma, as well as monoclonal antibody compositions.

Described herein are compositions and techniques related to generation and therapeutic application of artificial synapses. Artificial synapses are engineered extracellular vesicles, including exosomes, which incorporate sticky binders on their surface to anchor signaling domains against biological targets, such as receptors. These engineered additives can be organized in genetic vector constructs, expressed in mammalian cells, wherein the sticky binders attach to extracellular vesicles such as exosomes, thereby presenting their joined signaling domains which are rapidly taken up by recipient cells. Artificial synapses adopt the hallmark biophysical and biochemical features of extracellular vesicles, allowing for rapid deployment and scale-up. Importantly, this strategy can allow for kinetically favorable signal generation and signal propagation. This includes, for example, increasing density of agonist presentation to support receptor clustering an onerous barrier for traditional receptor targeting strategies.