Abstract: A method of immunizing against COVID-19 by administering a recombinant SARS-CoV2 protein-based vaccine, developed by either embedding the epitopes/domains, or chemically attaching, to an already established vaccine candidate, e.g., a detoxified recombinant tetanus neurotoxin (DrTeNT). The developed vaccine will have three novel contributions compared to the present vaccine technology: a) providing a novel and very effective vaccine platform; b) priming with DrTeNT will prepare the host immune system for better response; and c) oral delivery of the vaccine candidate with a group of neurotoxin binding proteins (NAPs) from Clostridium sp. A Detoxified recombinant tetanus neurotoxin (DrTeNT) is prepared by mutation of the active site amino acid residues is an effective vaccine candidate, and is used for embedding epitopes of SARS-CoV-2 virus protein for vaccination against Covid-19. DrTeNT is a risk-free vaccine, free of formalin or any other chemical adjuvants.

Abstract: The present disclosure provides a polynucleotide encoding the anti-PD-L1/anti-4-1BB bispecific antibody capable to effectively block the interactions between PD-L1 and its receptor PD-1 and between 4-1BB and its ligand. The bispecific antibody may have high binding affinity to both of a PD-L1 protein and a 4-1BB protein.

Abstract: The present disclosure provides water-soluble film packages composed of a water-soluble film, where the packages include: one or more compartment(s) including dehydrated microbes. The disclosure further provides methods of production of the water-soluble film packages, and methods of application thereof. The water-soluble packages of the disclosure enable convenient and accurate application of microbial dry powders to plants, promote uniform dispersion of powdered microbes, enhance microbial shelf life, and enhance the survival of microbes on seed, while being environmentally sustainable.

Abstract: The present disclosure provides non-intergeneric remodeled microbes that are able to fix atmospheric nitrogen and deliver such to plants in a targeted, efficient, and environmentally sustainable manner. The utilization of the taught microbial products will enable farmers to realize more productive and predictable crop yields without the nutrient degradation, leaching, or toxic runoff associated with traditional synthetically derived nitrogen fertilizer. The remodeled microbes taught herein are able to be combined with leading agricultural chemistry and elite germplasm. Furthermore, the disclosure provides seed treatments comprising remodeled microbes.

Abstract: The present disclosure relates generally to GLP-1 agonists and pharmaceutical compositions comprising the same, as well as methods for treating a GLP-1 associated disease, disorder, or condition.

Abstract: The invention provides compositions and methods for manufacturing adoptive cell therapies. In particular embodiments, the invention provides methods of harvesting populations of cells, isolating and activating PBMCs, expanding T cells, and administering the T cell therapeutic to a subject in need thereof.

Abstract: Provided herein are methods for, inter alia, separating and/or quantitating subpopulations of cells from a population of cells using simultaneous tagging methods. The methods provided are, inter alia, useful for analyzing and modulating selective cell populations as well as identification of targets for therapeutic purposes.

Abstract: Compositions, methods of making and methods of using are provided for topical administration of pharmaceutical compositions comprising one or more activin receptor-like kinase-5 (ALK-5) kinase inhibitors. The pharmaceutical compositions can be used for treatment of diseases and disorders affecting the skin.

Abstract: Methods are provided for assessing the nitrogen status of a plant or multiple plants in a plurality of plants, and optionally comparing the nutrient status to a plant or multiple plants in another plurality of plants (e.g., another plurality of plants in a different field or different region of the same field). The methods find utility, for example, in validating the performance of alternative plant nitrogen treatments such as validating the performance of nitrogen fixing microbes in replacing a defined amount of nitrogen from synthetic nitrogen treatment.

Abstract: Disclosed are methods for efficient fermentation broth recycle, methods for improving bottoms recycle, and methods for converting CO, CO2, and optionally H2 to ethanol and other oxygenated products, the methods comprising providing to a bioreactor a gaseous substrate comprising CO, CO2, and optionally H2, at least one acetogenic carboxydotrophic bacterium, and a liquid nutrient medium, and providing conditions within the bioreactor for the at least one acetogenic carboxydotrophic bacterium to convert CO, CO2, and optionally H2 to at least one oxygenated product. Also disclosed are methods for preparing animal feed and for preparing fertilizer.

Abstract: The present disclosure describes methods of treating conditions such as trigeminal neuralgia and pain related thereto. The methods of the present disclosure may include administering to a patient in need thereof a therapeutically effective amount of Trimeprazine or a pharmaceutically acceptable salt thereof, thereby treating the patient. The methods may include reducing a patient's pain as determined by patient-reported or clinician-delivered outcome assessments.

Abstract: The present description relates to methods for delivering polypeptide cargos from an extracellular space to the cytosol and/or nucleus of a target eukaryotic cell. The methods involve contacting the cell with the polypeptide cargo in the presence of a peptide shuttle agent at a concentration sufficient to increase the polypeptide cargo's transduction efficiency. Also described here are parameters that may be used in the rational design of such synthetic peptide shuttle agents, peptide shuttle agents that satisfy one or more of these design parameters, as well as methods and compositions relating to the use of the synthetic peptide shuttle agents for delivery of a variety of polypeptide cargos (such as transcription factors, antibodies, CRISPR-associated nucleases and functional genome editing complexes) from an extracellular space to the cytosol and/or nucleus of target eukaryotic cells. Applications and targets for genome-editing NK cells for improved immunotherapy are also described.

Abstract: The present disclosure relates to antibodies that bind human Dectin-1, multispecific (e.g., bispecific) binding molecules, and methods of use and production related thereto.

Abstract: The present disclosure provides compounds of the formulae herein (e.g., Formula (I), Formula (V)), and pharmaceutically acceptable salts thereof, which are useful for modulating protein synthesis (e.g., modulating synthesis of BCL-2, MYC, CCND1, MCL-1, ALK, KRAS-G12D). The present disclosure also provides pharmaceutical compositions and kits comprising the compounds, or pharmaceutically acceptable salts thereof, and methods of treating or preventing diseases or disorders (e.g., diseases or disorders associated with BCL-2, MYC, CCND1, MCL-1, ALK, KRAS-G12D) by administering to a subject in need thereof the compounds, or pharmaceutically acceptable salts thereof, or pharmaceutical compositions thereof.

Abstract: The disclosure provides interleukin 21 (IL-21) variants that have (i) decreased or no binding to a human interleukin 21 receptor (IL-21R) as compared to a wild-type human IL-21 polypeptide; or (ii) increased stability as compared to a wild-type human IL-21 polypeptide; or (iii) decreased or no binding to a human interleukin 21 receptor (IL-21R) as compared to a wild-type human IL-21 polypeptide and increased stability as compared to a wild-type human IL-21 polypeptide. The disclosure also provides fusion proteins including an antibody or fragment thereof bound, e.g., covalently linked, to an IL-21 variant.

Abstract: Systems and methods for monitoring and managing versioning changes to computational workflows caused by ongoing development of computational modules implemented within the computational workflows. Exemplary implementations may: store a workflow repository and a user repository; monitor the workflow repository to detect changes to computational modules included in the workflow repository; responsive to detections of changes to the computational modules, identify computational workflows defined by workflow definitions impacted by the detected changes; identify, based on information included in the user repository, users associated with the identified computational workflows; manage information defining user interfaces associated with individual users; update information defining the user interfaces based on the detected changes and the identified users; effectuate presentation of the user interfaces to the users; and/or other exemplary implementations.

Abstract: The compounds disclosed herein (e.g., compounds having a structure according to Formula (I/(II)/(III)/(IV), and (V)) are polymers wherein an organic polymeric segment (e.g., a polyethylene glycol (PEG) group) comprises covalent attachments to two or more lipid substructures, and each lipid substructure independently comprises a hydrophobic moiety and a hydrophilic moiety. The compounds provided herein can be useful for delivery and expression of mRNA and encoded protein, e.g., as a component of liposomal delivery vehicle, and accordingly can be useful for treating various diseases, disorders and conditions, such as those associated with deficiency of one or more proteins.

Abstract: The present invention provides, among other things, compositions and methods of formulating nucleic acid-containing nanoparticles comprising no more than three distinct lipids components, one distinct lipid component being a sterol-based cationic lipid. In some embodiments, the present invention provides compositions and methods in which the lipid nanoparticles further comprise helper lipids and PEG-modified lipids. The resulting formulation comprises a high encapsulation percentage for nucleic acids.

Abstract: Systems for plant culture include a chamber featuring one or more walls enclosing a spatial volume internal to the chamber, where the one or more walls include a surface for supporting a plant within the enclosed spatial volume, a gas delivery apparatus with at least one gas source, a nutrient delivery apparatus with a reservoir, a sampling apparatus connected to a port formed in the one or more walls, and a controller configured so that during operation of the system, the controller activates the nutrient delivery apparatus to deliver an aqueous growth medium to the plant, and activates the gas delivery apparatus to deliver into the enclosed spatial volume a mixture of isotopically-substituted gases. Also provided are methods of use of the system for measuring nitrogen in a plant and for identifying microbes capable of providing fixed nitrogen to a plant.

Abstract: The present invention is directed to a composition, mammalian cell and vector, and a method for the production of, and method of treatment with, a recombinant protein vaccine in a mammalian cell line. The methods and compositions are particularly useful for generating the stable expression of a recombinant protein vaccine of interest. The invention is particularly useful for the production of vaccines to aid in protection against viral pathogens for vertebrates, in particular mammalians, especially humans. The mammalian cell for producing a protein of interest comprises: a plasmid encoded with a nucleotide sequence encoding one or more epitopes or subunits of the SARS-CoV-2 that are embedded in the nucleotide sequence encoding a detoxified recombinant tetanus toxin (DrTeNT).