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 invention relates to design and therapeutic use of solubilized apyrase polypeptides, pharmaceuticals compositions, therapeutic uses and methods useful for preventing and treating tissue damage.

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.

Combinations of an apyrase and an annexin, including fusion proteins thereof, are synergistic antithrombotics that do not induce unwanted bleeding

Described herein are microbial probiotics that, in response to metabolite extracellular ATP (eATP) produced in the microenvironment of inflamed tissues detected, e.g., via an engineered mammalian P2Y2 receptor, secrete an anti-inflammatory protein, e.g., IL-2, IL-10, or the CD39-like eATP-degrading enzyme apyrase. Thus, provided herein is an isolated Saccharomyces cell (or cells, e.g., a population of such cells) that has been engineered to express one, two, or all three exogenous proteins selected from: (I) a mammalian P2Y purinoceptor 2 (P2Y2) protein, preferably human P2Y2; 15 (ii) a mutant Gpa1 protein comprising at least 5 C-terminal residues from a mammalian G alpha, preferably Gai3, wherein the mutant Gpa1 protein couples the P2Y2 protein to the yeast mating pathway; and (iii) an anti-inflammatory protein.

A genetically engineered strain having high-yield of L-valine is disclosed. Starting from Escherichia coli W3110, an acetolactate synthase gene alsS of Bacillus subtilis is inserted into a genome thereof and overexpressed; a ppGpp 3′-pyrophosphate hydrolase mutant R290E/K292D gene spoTM of Escherichia coli is inserted into the genome and overexpressed; a lactate dehydrogenase gene ldhA, a pyruvate formate lyase I gene pflB, and genes frdA, frdB, frdC, frdD of four subunits of fumaric acid reductase are deleted from the genome; a leucine dehydrogenase gene bcd of Bacillus subtilis replaces a branched chain amino acid transaminase gene ilvE of Escherichia coli; and an acetohydroxy acid isomeroreductase mutant L67E/R68F/K75E gene ilvCM replaces the native acetohydroxy acid isomeroreductase gene ilvC of Escherichia coli. Furthermore, the L-valine fermentation method is improved by using a two-stage dissolved oxygen control. The L-valine titer and the sugar-acid conversion rate are increased.

The present invention provides an ATP hydrolyzing enzyme, a nucleic acid encoding an ATP hydrolyzing enzyme, or host cells, microorganisms, such as bacteria, or viral particles comprising such nucleic acids encoding an ATP hydrolyzing enzyme for use in the treatment of dysbiosis or a dysbiosis-related disease.

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.

This invention provides composition and methods of treating subjects with microbial infection, sepsis, wounds, heterotopic ossification, or combination thereof. In each case, the treatment methods of the present invention comprise administering ADPase-enhanced apyrase agents, alone or in combination with an antimicrobial.

A kit for detecting bacterial ATP in a sample is provided. The kit comprises an aqueous composition having a pH of about 6.0 to 7.2. The aqueous composition comprises effective amounts of a polyol, a buffer reagent, a protein, and ATP-diphosphohydrolase. A method of using the kit to detect bacterial ATP is also provided.