11 results about "Constitutively active" patented technology

The invention relates to constitutively active mutants of the transcription factor TFEB, which can mutate the lysine of one or both sites of positions 219 and 347; and / or also mutate the glutamic acid of one or both sites of positions 221 and 349, in order to eliminate the SUMOylation of the protein. By replacing these residues either from positions 219 and / or 221 and / or 347 and / or 349 by any other amino acid (such as arginine or alanine), it gives rise to a mutated TFEB, which more actively induces the expression of genes and protein synthesis of the lysosomal and autophagic pathway. Such as lysosomal storage disorders, neurodegenerative diseases, liver diseases, muscle diseases and metabolic diseases, and / or disorders or processes in the aging of the skin.

Provided herein are constitutively active chimeric cytokine receptors (CACCRs). Such CACCRs allow for increased immune cell activation, proliferation, persistence, and / or potency when present on immune cells bearing chimeric antigen receptors (CARs). Also provided are methods of making and using the CACCRs described herein.

A method of treating pancreatic adenocarcinoma in an individual is disclosed. The method involves administering to the individual a therapeutically effective amount of a therapeutic agent comprising recombinant acid sphingomyelinase. In one embodiment, the therapeutic agent further includes one or more compositions selected from the group consisting of modified enzymes, fusion proteins and constitutively active mutants. In another embodiment, the therapeutic agent further includes a pharmaceutically acceptable excipient.

This disclosure is based, at least in part, on the unexpected discovery that genetically modified pluripotent stem cells having a constitutively active stem cell factor (SCF) can differentiate into enucleated red blood cells, self-renew, and expand in culture media for an extended period of time. Accordingly, the disclosed methods enable large-scale production of red blood cells with significantly reduced overall cost as compared to the existing methods.

Constitutively active cyclic GMP-AMP Synthase (cGAS) proteins are provided. Nucleic acid molecules encoding the constitutively active proteins as well as pharmaceutical compositions comprising the constitutively active proteins are also provided. Methods of inducing an immune response against a target cell and treating cancer are also provided.

The present invention relates to a set of constitutively active pro-inflammatory caspases comprising shuffled p10 and p20 domains for use in a method of stimulating an immune response in a subject. The present invention also relates to an immunostimulatory composition comprising said constitutively active pro-inflammatory caspases comprising shuffled p10 and p20 domains, with a pharmacologically acceptable excipient, and to its use in a method of treating a subject.

Disclosed are nucleic acid constructs comprising a nucleic acid sequence encoding a vitelliform macular dystrophy-2 (VMD2) promoter operably linked to a nucleic acid sequence encoding Rap1a. Disclosed are vectors comprising the nucleic acid constructs disclosed herein. Disclosed are compositions comprising the disclosed nucleic acid constructs or vectors. Also disclosed are methods of treating a subject having age-related macular degeneration comprising administering one or more of the disclosed nucleic acid constructs, vectors, or compositions to a subject in need thereof.

A composition may have an adeno-associated virus (AAV) vector containing a nucleic acid sequence encoding NFAT1 (Nuclear Factor of Activated T Cells 1) protein for treatment of osteoarthritis and other joint diseases. The AAV vector may be AAV serotype 5, other AAV serotypes, and AAV subtype variants. The nucleic acid sequence encoding NFAT1 may be constitutively active NF ATI or wild-type NF ATI. The nucleic acid sequence encoding NFAT 1 may comprise a hemagglutinin epitope tag. At least one AAV vector may comprise a viral genome concentration of about 2x1010 viral genomes. The NFAT 1 may be human NFAT1. The NFAT1 may be mouse NFAT1. A pharmaceutical composition may comprise the composition and a pharmaceutically acceptable carrier. The pharmaceutically acceptable carrier may be suitable for intra-articular or local tissue injection. The pharmaceutically acceptable carrier may be sterile saline.

The present invention includes methods for treating a human patient with Crenolanib, wherein the human patient is suffering from a FLT3 mutated leukemia, the method comprising: determining that the human patient has a poor prognosis by: obtaining or having obtained a leukemia biological sample and performing or having performed a genotyping assay on the biological sample to determine that the human patient has both a mutated FLT3 or a constitutively active FLT3 mutant and one or more driver mutations in one or more epigenetic regulator proteins that results in a loss of normal function of the epigenetic regulator proteins which, indicates that the patient has a poor prognosis; and administering to the patient determined to have the poor prognosis a therapeutically effective amount of Crenolanib, or a pharmaceutically acceptable salt thereof having the formula:to treat the leukemia.

Modified Tregs including DNA constructs encoding (1) chimeric antigen receptor (CAR), (2) at least one of IL-2, IL-2 mutein, or constitutively active STAT5B (STAT5B-CA) or STAT5A (STAT5A-CA), and (3) optionally a "neurodegenerative disease-modifying molecule" (NDMM) or "disease-modifying molecule" (DMM) are described. DNA encoding (1), (2) and optionally (3) is on the same or different constructs; (ii) expression (1), (2) and optionally (3) is controlled by inducible or constitutive promoters; (iii) the described Treg inducibly or constitutively expresses IL-2, IL-2 mutein, or STAT5B-CA or STAT5A-CA, the CAR, and optionally a DMM or NDMM in vivo; and (iv) the Treg persists longer and / or in greater numbers in the CNS and / or spleen compared to Tregs expressing the same CAR without exogenous DNA encoding IL-2, IL-2 mutein or STAT5B-CA or STAT5A-CA. CAR DNA constructs used to produce such modified Tregs and uses thereof for treatment of neurodegenerative diseases are also described.

Disclosed is a nucleic acid construct comprising a nucleic acid sequence encoding a vitelloid macular dystrophy 2 (VMD2) promoter operably linked to a nucleic acid sequence encoding Rap1a. Disclosed is a vector comprising the nucleic acid construct disclosed herein. Disclosed is a composition comprising a nucleic acid construct or vector of the present disclosure. Also disclosed is a method of treating a subject with age-related macular degeneration, comprising administering one or more of the nucleic acid constructs, vectors, or compositions of the present disclosure to a subject in need thereof.