Patent classifications
C12Y106/03001
Compositions for Treatment of Vascular Disease
Provided are various embodiments relating to compositions and methods for treating vascular disease, including core NOX1 promoters and variants thereof for regulating expression of transgenes in response to vascular pathology and allowing for increased transgene loading capacity. Also provided are variant FOXP polypeptides having a zinc finger and leucine zipper region of a different FOXP polypeptide. Further provided are vectors comprising the core NOX1 promoters and/or a coding sequence for variant FOXP polypeptides described herein and optionally coding sequence(s) for one or more additional therapeutic polypeptide(s), such as IL10, for treating inflammation-associated diseases, such as vascular disease. Also provided is a screening model for testing therapeutic agents capable of treating established and ongoing atherosclerotic pathology.
TREATMENT OF CHRONIC GRANULOMATOUS DISEASE
The present invention relates to an isolated human hematopoietic stem cell or progenitor cell, transduced with a lentiviral vector which comprises a coding nucleic acid sequence encoding a functional variant of a polypeptide selected from gp9lphox, p22phox, p40phox, p47phox, p67phox and Rac2; under transcriptional control of a promoter sequence that comprises or essentially consists of the miR223 promoter sequence (SEQ ID NO 01).
LENTIVIRAL VECTORS IN HEMATOPOIETIC STEM CELLS TO TREAT X-LINKED CHRONIC GRANULOMATOUS DISEASE
In certain embodiments a lentiviral vector for the treatment of X-linked chronic granulomatous disease (X-CGD) is provided. In certain embodiments the vector comprises an expression cassette comprising a nucleic acid construct comprising a CYBB promoter or effective fragment thereof; and a nucleic acid that encodes gp91.sup.phox operably linked to the CYBB promoter or promoter fragment.
Diagnosis and therapy of multiple sclerosis
The serotonin receptor 5HT2A (5HT2aR) and membrane NADPH oxidases (NOX enzymes) are found to be a target of autoantibodies present in Multiple Sclerosis patients. The present invention refers to peptides comprised in the extracellular regions of the human 5HT2aR and/or NOXs for diagnosis and therapy of Multiple Sclerosis.
ENZYME SCAFFOLDS AND METHODS OF USE
Polypeptide scaffolds comprising enzymatic proteins are provided. The enzymatic polypeptide scaffolds comprise heterologous enzymes to form a heterologous metabolic pathway, and can be targeted to a substrate through a surface anchoring domain. The enzymatic polypeptide scaffolds leverage the high specificity and affinity protein/protein interaction between the cohesins and dockerins of microorganismal cellulosomes to form custom enzymatic arrays.
METHODS FOR DECOUPLING YIELD AND PRODUCTIVITY OF A NON-CATABOLIC COMPOUND PRODUCED BY A HOST CELL
Provided herein are compositions and methods for uncoupling the yield and productivity of an isoprenoid compound produced in a host cell. In some embodiments, the yield and productivity are uncoupled by genetically modifying the host cell to reduce flux through the citric acid cycle (TCA). In other embodiments, the yield and productivity are uncoupled by reducing the levels of ATP in the host cell.
OXIDASE-BASED CHEMILUMINESCENCE ASSAY OF PHAGOCYTIC LEUKOCYTES IN WHOLE BLOOD AND BODY FLUIDS APPLICABLE TO POINT-OF-CARE (POC) DIAGNOSTIC TESTING POINT-OF-CARE (POC) MEASUREMENT OF ABSOLUTE NEUTROPHIL FUNCTION (ANF)
A method for estimating a number of phagocytes in a body fluid of an animal includes stimulating NADPH oxidase activity of the phagocytes; and quantifying a resulting reductive deoxygenation of a chemiluminigenic substrate by an emitted chemiluminescence of the chemiluminigenic substrate using an instrument capable of measuring light. The NADPH oxidase activity of the phagocytes is preferably stimulated by an immunologic or chemical capable of activating a respiratory burst by the phagocytes, and by a stimulus in solution or coated to a surface contacted by the phagocytes. The stimulus is preferably phorbol myristate acetate (PMA). The animal is preferably human, and the body fluid is preferably blood and/or spinal fluid. The phagocytes are preferably neutrophil leukocytes, and the chemiluminigenic substrate is preferably lucigenin (N,N′-dimethyl-9,9′-biacridinium dinitrate). Also provided is a method of treatment based on the estimation method.
PLANT CELLS AND PLANTS MODIFIED TO INCREASE RESISTANCE TO NECROTROPHS OR DROUGHT AND METHODS OF SELECTING AND USING THE SAME
The invention generally relates to plant cells and plants modified to increase resistance to necrotrophs or drought and methods of selecting and using the same. More specifically, the invention relates in part to plant cells and/or plants modified to eliminate or reduce as compared to control plants cell the NADPH oxidase activity or expression of certain respiratory burst oxidase homolog (RBOH) proteins and methods of selecting for and using the same.
Compositions and methods for the production of pyruvic acid and related products using dynamic metabolic control
The present disclosure is related to genetically engineered microbial strains and related bioprocesses for the production of pyruvate and related products. Specifically, the use of dynamically controlled synthetic metabolic valves to reduce the activity of enzymes known to contribute to pyruvate synthesis, leads to increased pyruvate production in a two-stage process rather than a decrease in production.
CONDITIONING METHODS FOR GENE THERAPY
The disclosure provides compositions and methods useful for the depletion of a specific population of endogenous hematopoietic stem cells and/or immune cells from a subject prior to transplantation with genetically modified stem cells to improve the engraftment of the transplanted stem cells and provide gene therapy. The disclosure provides compositions and methods for the treatment of various hematopoietic diseases, metabolic disorders, cancers, and autoimmune diseases, among others. Described herein are antibodies, antigen-binding fragments, and conjugates thereof that can be applied to effect the treatment of these conditions, for instance, by depleting a population of CD117+ or CD45+ cells in a patient, such as a human.