21 results about "Constitutively active" patented technology

Disclosed are methods of treating an eye disease by administering a recombinant adeno-associated virus (AAV) vector that encodes the proteoglycan decorin to the eye of a subject. Also provided are animal models of glaucoma that are generated using a recombinant AAV vector that encodes a constitutively active variant of transforming growth factor beta 2 (TGFβ2CS).

Novel methods for producing self-renewing erythroblasts (SREs) from induced pluripotent stem cells (iPSCs) or CD34+ cells are provided. Also provided are genetically modified iPSCs or CD34+ cells having a constitutively active stem cell factor (SCF) receptor and a constitutively active Janus kinase 2 (JAK2) that can differentiate into enucleated red blood cells, self-renew, and expand in culture media for an extended period of time. In particular, the disclosed methods completely eliminate the need for SCF and Epo.

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.

The present invention includes methods for treating a proliferative disorder in a subject with mutated or constitutively active FLT3 in a subject relapsed / refractory to one or more prior tyrosine kinase inhibitors comprising: obtaining a tumor sample from the subject that is relapsed / refractory to one or more prior tyrosine kinase inhibitors; measuring expression of mutated or constitutively active FLT3 mutant in the tumor sample; and administering to the subject a therapeutically effective amount of crenolanib or a pharmaceutically acceptable salt thereof sufficient to treat the proliferative disorder.

The present disclosure relates to compositions for expression of a constitutively-active cyclic GMP-AMP synthase in cells of a mammalian subject and uses thereof for enhancing immunogenicity of mRNA vaccines. The mRNA may be encapsulated in a lipid nanoparticle (LNP) or may be complexed with a lipid (RNA-Lipoplex). The present disclosure also relates to compositions further comprising a pathogen recognition receptor agonist.

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 disclosure relates to compositions for expression of a constitutively-active cyclic GMP-AMP synthase in cells of a mammalian subject and uses thereof for enhancing immunogenicity of mRNA vaccines. The mRNA may be encapsulated in a lipid nanoparticle (LNP) or may be complexed with a lipid (RNA-Lipoplex). The present disclosure also relates to compositions further comprising one or both of a lysophosphatidylcholine (LPC) compound and a pathogen recognition receptor agonist.

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.

The present invention relates to a cell comprising a chimeric antigen receptor (CAR) and a constitutively active or inducible Signal Transducer and Activator of Transcription (STAT) molecule.

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.

Novel methods for producing self-renewing erythroblasts (SREs) from induced pluripotent stem cells (iPSCs) or CD34+ cells are provided. Also provided are genetically modified iPSCs or CD34+ cells having a constitutively active stem cell factor (SCF) receptor and a constitutively active Janus kinase 2 (JAK2) that can differentiate into enucleated red blood cells, self-renew, and expand in culture media for an extended period of time. In particular, the disclosed methods completely eliminate the need for SCF and Epo.

The present invention includes methods for treating a proliferative disorder in a subject with mutated or constitutively active FLT3 in a subject relapsed / refractory to one or more prior tyrosine kinase inhibitors comprising: obtaining a tumor sample from the subject that is relapsed / refractory to one or more prior tyrosine kinase inhibitors; measuring expression of mutated or constitutively active FLT3 mutant in the tumor sample; and administering to the subject a therapeutically effective amount of crenolanib or a pharmaceutically acceptable salt thereof sufficient to treat the proliferative disorder.

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.

Disclosed is a platform for fluorescence imaging of bulk RNA dynamics in living cells. The platform utilizes a technique including exposing a plurality of live cells configured to overexpress a WT or mutant ribonucleoside kinase UCK2 under control of an inducible promoter, a constitutively active promoter, or both, to a first quantity of a fluorescent nucleoside (such as fluorescent bicyclic and tricyclic cytidine analogues) for a first period of time.

The disclosure provides methods for treating estrogen receptor positive (ER+) cancer other than breast and ovarian cancer, including cancer that has acquired gain of function mutations in the ligand binding domain of the Estrogen Receptor 1 (ESR1) gene, which encodes the ERα receptor protein. The methods comprise administering an effective amount of lasofoxifene, a pharmaceutically acceptable salt thereof, or a prodrug thereof. The disclosure describes the detection of the (ESR1) gene mutations that lead to endocrine resistance in such cancers.

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.