The present disclosure provides zinc finger fusion proteins that inhibit expression of Nav1.7 in the nervous system, and methods of using the proteins to treat pain disorders.
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
Disclosed herein are methods and compositions for inactivating MHC genes, using zinc finger nucleases (ZFNs) comprising a zinc finger protein and a cleavage domain or cleavage half-domain in conditions able to preserve cell viability. Polynucleotides encoding ZFNs, vectors comprising polynucleotides encoding ZFNs and cells comprising polynucleotides encoding ZFNs and/or cells comprising ZFNs are also provided.
C07K 14/74 - Major histocompatibility complex [MHC]
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
The disclosure provides the methods of detecting an anti-lysosomal enzyme antibody in a human subject (e.g., in the presence of a circulating lysosomal enzyme) and the methods of improving an efficacy of an anti-lysosomal enzyme antibody assay (e.g., improving the assay sensitivity and the circulating lysosomal enzyme tolerance), comprising pre-treating the biological sample of the subject with a base at pH of about 11 or greater and measuring the presence of the anti-lysosomal enzyme antibody in the biological sample of the subject.
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
G01N 33/543 - ImmunoassayBiospecific binding assayMaterials therefor with an insoluble carrier for immobilising immunochemicals
G01N 33/544 - ImmunoassayBiospecific binding assayMaterials therefor with an insoluble carrier for immobilising immunochemicals the carrier being organic
4.
Antigen Binders Specific For IL-23R And Uses Thereof
IL23R overexpression has been described as a common feature of pathogenic inflammatory cells involved in the onset and maintenance of autoimmune diseases and chronic inflammation. The present disclosure relates to a novel antigen binder directed to IL-23R, to compositions that comprise said antigen binder, and to the use of said antigen binder. The present disclosure further relates to fusion proteins comprising said antigen binder, such as, for example, chimeric antigen receptors.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
Provided herein are base editor systems comprising fusion proteins that comprise zinc finger protein and cytidine deaminase domains, as well as methods of using the base editor systems. The systems can be used to specifically alter a single base pair in a target DNA sequence.
C12N 15/90 - Stable introduction of foreign DNA into chromosome
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C12N 15/62 - DNA sequences coding for fusion proteins
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A61K 9/00 - Medicinal preparations characterised by special physical form
The present disclosure relates to the methods for treating or ameliorating one or more symptoms of Fabry disease, reducing the amount of glycosphingolipids, and/or increasing an α galactosidase A (α-Gal A) protein activity in a subject in need thereof by administering the expression vectors (e.g., an AAV expression vector) comprising an α galactosidase A (α-Gal A) expression cassette, which comprises an α galactosidase A (α-Gal A) transgene encoding the at least one α-Gal A protein at a dose of about 5×1012 vector genomes per kilogram of body weight (vg/kg) to about 5×1013 vg/kg.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
A61K 31/573 - Compounds containing cyclopenta[a]hydrophenanthrene ring systemsDerivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
A61K 38/47 - Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
Methods and compositions for modifying T-cells in which PD1 and/or CTLA-4 is repressed and/or inactivated using fusion proteins such as artificial transcription factors and nucleases.
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
C12N 5/10 - Cells modified by introduction of foreign genetic material, e.g. virus-transformed cells
11.
METHODS AND COMPOSITIONS FOR THE TREATMENT OF RARE DISEASES
The present disclosure is in the field of modulation of genes involved in rare diseases including for diagnostics and therapeutics for rare diseases such as Angelman's Syndrome, Facioscapulohumeral Muscular Dystrophy (FHMD), Amyotrophic Lateral Sclerosis (ALS), Frontotemporal dementia (FTD) and Spinal Muscular Atrophy (SMA).
A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
The present disclosure provides compositions and methods for modulating transcription of mutant C9orf72 gene alleles in patients in need thereof, including patients having a C9orf72-related disease such as amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD).
C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
A61P 25/00 - Drugs for disorders of the nervous system
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
The present disclosure provides compositions and methods for modulating transcription of mutant C9orf72 gene alleles in patients in need thereof, including patients having a C9orf72-related disease such as amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD).
C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
A61P 25/00 - Drugs for disorders of the nervous system
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
The present disclosure provides methods and compositions to develop AAV capsids with a desired characteristic compared to a natural AAV serotype. These capsids are useful, for example, for the delivery of genome engineering molecules and gene therapy molecules for the treatment of a subject in need thereof.
C07K 7/08 - Linear peptides containing only normal peptide links having 12 to 20 amino acids
C12N 7/00 - Viruses, e.g. bacteriophagesCompositions thereofPreparation or purification thereof
C12N 7/01 - Viruses, e.g. bacteriophages, modified by introduction of foreign genetic material
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
C12N 15/66 - General methods for inserting a gene into a vector to form a recombinant vector using cleavage and ligationUse of non-functional linkers or adaptors, e.g. linkers containing the sequence for a restriction endonuclease
C12Q 1/6897 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids involving reporter genes operably linked to promoters
C40B 20/04 - Identifying library members by means of a tag, label, or other readable or detectable entity associated with the library members, e.g. decoding processes
Disclosed herein are zinc finger nucleases for cleaving a CIITA gene, polynucleotides encoding the same, and methods of using the zinc finger nucleases to modulate the expression of a CIITA gene. Also provided is a cell modified by the zinc finger nucleases and uses of the cell to treat a disease.
Described herein are engineered nucleases comprising mutations in the cleavage domain (e.g., FokI or homologue thereof) and/or DNA binding domain (zinc finger protein, TALE, single guide RNA) such that on-target specificity is increased.
The present invention provides compositions comprising a recombinant AAV and one or more pharmaceutically acceptable excipients. The compositions have improved stability and shelf life as compared to other AAV compositions.
Provided herein are base editor systems comprising fusion proteins that comprise zinc finger protein and cytidine deaminase domains, as well as methods of using the base editor systems. The systems can be used to specifically alter a single base pair in a target DNA sequence.
The present disclosure provides zinc finger fusion proteins that inhibit expression of alpha-synuclein in the nervous system, and methods of using the proteins to treat Parkinsons disease, Lewy body dementia, multiple system atrophy, Alzheimers disease, and other neurodegenerative diseases.
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
The disclosure provides the enzyme and non-enzyme replacement therapies for treating Fabry disease in a human subject, determined based on measuring the presence or absence of an anti-α-Galactosidase A (GLA) neutralizing antibody in a biological sample of the subject, as measured by an anti-GLA neutralizing antibody assay.
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving proteins, peptides or amino acids
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
A61K 31/445 - Non-condensed piperidines, e.g. piperocaine
A61K 31/439 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
22.
METHODS AND COMPOSITIONS FOR TREATMENT OF A GENETIC CONDITION
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
23.
Methods and compositions for treating Huntington's Disease
Disclosed herein are compositions comprising non-naturally occurring zinc finger domains, fusion proteins comprising these zinc finger domains, polynucleotides encoding these proteins, cells expressing these proteins and pharmaceutical compositions comprising these proteins or polynucleotides as well as methods of modifying an Htt gene using these compositions for treating or preventing Huntington's Disease.
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C12N 15/90 - Stable introduction of foreign DNA into chromosome
24.
GENERATION OF CD4+ EFFECTOR AND REGULATORY T CELLS FROM HUMAN PLURIPOTENT STEM CELLS
The disclosure relates to total antibody assays, including screening assays and confirmatory assays, for the detection of anti-AAV (e.g. anti-AAV6) antibodies in a subject as it relates to pre- and post-treatment total antibody levels. The disclosure also relates to methods of treating a subject with a gene therapy comprising a rAAV (e.g. rAAV6) vector.
A61K 35/42 - Respiratory system, e.g. lungs, bronchi or lung cells
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
Disclosed herein are methods and compositions for inactivating TCR genes, using zinc finger nucleases (ZFNs) comprising a zinc finger protein and a cleavage domain or cleavage half-domain in conditions able to preserve cell viability. Polynucleotides encoding ZFNs, vectors comprising polynucleotides encoding ZFNs and cells comprising polynucleotides encoding ZFNs and/or cells comprising ZFNs are also provided. Disclosed herein are also methods and compositions for expressing a functional exogenous TCR in the absence of endogenous TCR expression in T lymphocytes, including lymphocytes with a central memory phenotype. Polynucleotides encoding exogenous TCR, vectors comprising polynucleotides encoding exogenous TCR and cells comprising polynucleotides encoding exogenous TCR and/or cells comprising exogenous TCR are also provided.
Nucleases and methods of using these nucleases for inserting a sequence encoding a therapeutic IDUA or IDS protein such as an enzyme into a cell, thereby providing proteins or cell therapeutics for treatment and/or prevention of MPS I or MPS II disease.
A61K 38/47 - Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
C12N 15/90 - Stable introduction of foreign DNA into chromosome
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
The present disclosure provides expression constructs comprising a phenylalanine hydroxylase (PAH) transgene and methods of using the constructs for treating phenylketonuria (PKU).
Disclosed herein are methods and compositions for inactivating TCR and/or HLA genes, using engineered nucleases comprising at least one DNA binding domain and a cleavage domain or cleavage half-domain in conditions able to preserve cell viability. Polynucleotides encoding nucleases, vectors comprising polynucleotides encoding nucleases and cells comprising polynucleotides encoding nucleases and/or cells comprising nucleases are also provided.
A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
The present disclosure provides zinc finger fusion proteins that inhibit expression of tau in the nervous system, and methods of using the proteins to treat neurodegenerative diseases such as Alzheimer's disease, frontotemporal dementia, and other tauopathies.
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
35.
LIVER-SPECIFIC CONSTRUCTS, FACTOR VIII EXPRESSION CASSETTES AND METHODS OF USE THEREOF
Described herein are engineered nucleases comprising mutations in the cleavage domain (e.g., FokI or homologue thereof) and/or DNA binding domain (zinc finger protein, TALE, single guide RNA) such that on-target specificity is increased.
The present disclosure provides 2-in-1 zinc finger nuclease variants and methods of treating and/or preventing a lysosomal storage disorder using said zinc finger nuclease variants.
The present disclosure provides zinc finger fusion proteins that inhibit expression of the prion gene in the nervous system, and methods of using the proteins to treat prion disease.
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
Methods and compositions for modifying T-cells in which PD1 and/or CTLA-4 is repressed and/or inactivated using fusion proteins such as artificial transcription factors and nucleases.
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
C12N 5/0783 - T cellsNK cellsProgenitors of T or NK cells
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
C12N 5/10 - Cells modified by introduction of foreign genetic material, e.g. virus-transformed cells
Provided herein are genetically engineered mammalian stem and progenitor cells that have increased potential to differentiate into regulatory T cells. Also provided are methods of making and use thereof.
A61K 35/17 - LymphocytesB-cellsT-cellsNatural killer cellsInterferon-activated or cytokine-activated lymphocytes
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
Disclosed herein are polypeptides, polynucleotides encoding, cells and organisms comprising novel DNA-binding domains, including TALE DNA-binding domains. Also disclosed are methods of using these novel DNA-binding domains for modulation of gene expression and/or genomic editing of endogenous cellular sequences.
The present disclosure provides zinc finger fusion proteins that inhibit expression of alpha-synuclein in the nervous system, and methods of using the proteins to treat Parkinson's disease, Lewy body dementia, multiple system atrophy, Alzheimer's disease, and other neurodegenerative diseases.
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Disclosed herein are methods and compositions for inactivating TCR genes, using engineered nucleases comprising at least one DNA binding domain and a cleavage domain or cleavage half-domain in conditions able to preserve cell viability. Polynucleotides encoding nucleases, vectors comprising polynucleotides encoding nucleases and cells comprising polynucleotides encoding nucleases and/or cells comprising nucleases are also provided. Disclosed herein are also methods and compositions for expressing a functional exogenous TCR in the absence of endogenous TCR expression in T lymphocytes, including lymphocytes with a central memory phenotype. Polynucleotides encoding exogenous TCR, vectors comprising polynucleotides encoding exogenous TCR and cells comprising polynucleotides encoding exogenous TCR and/or cells comprising exogenous TCR are also provided.
Nucleases and methods of using these nucleases for inserting a sequence encoding a therapeutic α-Gal A protein such as an enzyme into a cell, thereby providing proteins or cell therapeutics for treatment and/or prevention of Fabry disease.
Board of Regents, The University of Texas System (USA)
Inventor
Gregory, Philip D.
Cooper, Laurence J.N.
Torikai, Hiroki
Abstract
Disclosed herein are methods and compositions for modulating the expression of a HLA locus, including Natural Killer (NK) cells that lack expression of one or more classic HLA genes and comprise one or more exogenous sequences that express one or more non-classic HLA gene.
Disclosed herein are methods and compositions for inactivating MHC genes, using zinc finger nucleases (ZFNs) comprising a zinc finger protein and a cleavage domain or cleavage half-domain in conditions able to preserve cell viability. Polynucleotides encoding ZFNs, vectors comprising polynucleotides encoding ZFNs and cells comprising polynucleotides encoding ZFNs and/or cells comprising ZFNs are also provided.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
Disclosed herein are engineered cleavage half-domains; fusion polypeptides comprising these engineered cleavage half-domains; polynucleotides encoding the engineered cleavage half-domains and fusion proteins; and cells comprising said polynucleotides and/or fusion proteins. Also described are methods of using these polypeptides and polynucleotides, for example for targeted cleavage of a genomic sequence.
C12N 15/52 - Genes encoding for enzymes or proenzymes
C12N 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C07K 7/06 - Linear peptides containing only normal peptide links having 5 to 11 amino acids
51.
HTT repressors comprising a zinc-finger protein transcription factor
Disclosed herein are HTT repressors and methods and compositions for use of these HTT repressors. Disclosed herein are methods and compositions for diagnosing, preventing and/or treating Huntington's Disease. In particular, provided herein are methods and compositions for modifying (e.g., modulating expression of) an HD HTT allele so as to prevent or treat Huntington Disease, including mHTT repressors (that repress mHTT transcripts and thus also repress mHTT protein expression).
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C12N 5/077 - Mesenchymal cells, e.g. bone cells, cartilage cells, marrow stromal cells, fat cells or muscle cells
C12N 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
A61K 35/12 - Materials from mammalsCompositions comprising non-specified tissues or cellsCompositions comprising non-embryonic stem cellsGenetically modified cells
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
Described herein are engineered nucleases specific for PD1 gene target sites, the nucleases comprising mutations in the cleavage domain (e.g., FokI or homologue thereof) and/or DNA binding domain (zinc finger protein, TALE, single guide RNA) such that on-target specificity for PD1 gene target sites is increased.
Nucleases and methods of using these nucleases for expressing a transgene from a safe harbor locus in a secretory tissue, and clones and animals derived therefrom.
Disclosed herein are compositions comprising non-naturally occurring zinc finger domains, fusion proteins comprising these zinc finger domains, polynucleotides encoding these proteins, cells expressing these proteins and pharmaceutical compositions comprising these proteins or polynucleotides as well as methods of modifying an Htt gene using these compositions for treating or preventing Huntington's Disease.
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C12N 15/90 - Stable introduction of foreign DNA into chromosome
58.
METHODS AND COMPOSITIONS FOR MODIFICATION OF A HLA LOCUS
Board of Regents, The University of Texas System (USA)
Inventor
Collingwood, Trevor
Cooper, Laurence J.N.
Gregory, Philip D.
Holmes, Michael C.
Miller, Jeffrey C.
Rebar, Edward J.
Reik, Andreas
Urnov, Fyodor
Abstract
Disclosed herein are methods and compositions for modulating the expression of a HLA locus or for selectively deleting or manipulating a HLA locus or HLA regulator.
Disclosed herein are compositions for linking DNA binding domains and cleavage domains (or cleavage half-domains) to form non-naturally occurring nucleases. Also described are methods of making and using compositions comprising these linkers.
The present disclosure provides methods for the separation and quantification of empty and full viral capsids (e.g., AAV capsids) within a viral preparation, such as a viral pharmaceutical composition or drug product.
C12N 7/00 - Viruses, e.g. bacteriophagesCompositions thereofPreparation or purification thereof
B01D 15/00 - Separating processes involving the treatment of liquids with solid sorbentsApparatus therefor
B01D 15/16 - Selective adsorption, e.g. chromatography characterised by constructional or operational features relating to the conditioning of the fluid carrier
B01D 15/36 - Selective adsorption, e.g. chromatography characterised by the separation mechanism involving ionic interaction, e.g. ion-exchange, ion-pair, ion-suppression or ion-exclusion
B01D 15/42 - Selective adsorption, e.g. chromatography characterised by the development mode, e.g. by displacement or by elution
The present disclosure provides methods and compositions to develop AAV capsids with a desired characteristic compared to a natural AAV serotype. These capsids are useful, for example, for the delivery of genome engineering molecules and gene therapy molecules for the treatment of a subject in need thereof.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
C07K 7/08 - Linear peptides containing only normal peptide links having 12 to 20 amino acids
C07K 14/005 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from viruses
C12N 7/00 - Viruses, e.g. bacteriophagesCompositions thereofPreparation or purification thereof
C12N 7/01 - Viruses, e.g. bacteriophages, modified by introduction of foreign genetic material
C12Q 1/6897 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids involving reporter genes operably linked to promoters
C40B 20/04 - Identifying library members by means of a tag, label, or other readable or detectable entity associated with the library members, e.g. decoding processes
63.
Controlled transgene expression in regulatory t cells
The present disclosure provides mammalian cells such as regulatory T cells containing a transgene in the FOXP3 genomic locus. Also provided are methods of generating the cells and methods of using the cells to treat patients in need of immunosuppression.
The present disclosure provides compositions and methods for modulating transcription of mutant C9orf72 gene alleles in patients in need thereof, including patients having a C9orf72-related disease such as amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD).
C07K 14/435 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A61P 25/00 - Drugs for disorders of the nervous system
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Described herein are engineered nucleases comprising mutations in the cleavage domain (e.g., FokI or homologue thereof) and/or DNA binding domain (zinc finger protein, TALE, single guide RNA) such that on-target specificity is increased.
Disclosed herein are compositions for linking DNA binding domains and cleavage domains (or cleavage half-domains) to form non-naturally occurring nucleases with alternative configurations. Also described are methods of making and using compositions comprising these linkers.
Disclosed herein are methods and compositions for targeted deletion of double-stranded DNA. The compositions include fusion proteins comprising a cleavage domain (or cleavage half-domain) and an engineered zinc finger domain, and polynucleotides encoding same. Methods for targeted deletion include introduction of such fusion proteins, or polynucleotides encoding same, into a cell such that two targeted cleavage events occur. Subsequent cellular repair mechanisms result in deletion of sequences between the two cleavage sites.
C12N 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
Nucleases and methods of using these nucleases for expressing an antibody from a safe harbor locus in a secretory tissue, and clones and animals derived therefrom.
A61K 35/12 - Materials from mammalsCompositions comprising non-specified tissues or cellsCompositions comprising non-embryonic stem cellsGenetically modified cells
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
C07K 16/32 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against translation products from oncogenes
A61K 35/28 - Bone marrowHaematopoietic stem cellsMesenchymal stem cells of any origin, e.g. adipose-derived stem cells
C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
C07K 16/30 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
C12N 15/62 - DNA sequences coding for fusion proteins
A61K 39/00 - Medicinal preparations containing antigens or antibodies
70.
Methods and compositions for targeted single-stranded cleavage and targeted integration
Disclosed herein are methods and compositions for generating a single-stranded break in a target sequence, which facilitates targeted integration of one or more exogenous sequences.
C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving virus or bacteriophage
C12N 15/90 - Stable introduction of foreign DNA into chromosome
C12Q 1/689 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms for bacteria
Described herein are methods and compositions for treating MPS I (Hurler/Hurler-Scheie/Scheie Syndrome) by administering to the subject a composition comprising a iduronidase (IDUA) polynucleotide. In one aspect, provided is a method of reducing, delaying and/or eliminating one or more of the need for additional treatment procedures, the onset, progression and/or severity of symptoms in a subject with MPS I, by administering to the subject a composition comprising a iduronidase (IDUA) polynucleotide.
G01N 33/66 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing involving blood sugars, e.g. galactose
C12Q 1/34 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase
A61K 38/47 - Hydrolases (3) acting on glycosyl compounds (3.2), e.g. cellulases, lactases
The present disclosure provides expression constructs comprising a GLA transgene encoding the at least one α-Gal A protein for use in expressing α-Gal A proteins and preventing, inhibiting or treating Fabry disease or one or more symptoms associated with Fabry disease.
Nucleases and methods of using these nucleases for inserting a sequence encoding a therapeutic protein such as an enzyme into a cell, thereby providing proteins or cell therapeutics for treatment and/or prevention of a lysosomal storage disease.
A01N 63/00 - Biocides, pest repellants or attractants, or plant growth regulators containing microorganisms, viruses, microbial fungi, animals or substances produced by, or obtained from, microorganisms, viruses, microbial fungi or animals, e.g. enzymes or fermentates
C12N 15/90 - Stable introduction of foreign DNA into chromosome
Disclosed herein are engineered cleavage half-domains; fusion polypeptides comprising these engineered cleavage half-domains; polynucleotides encoding the engineered cleavage half-domains and fusion proteins; and cells comprising said polynucleotides and/or fusion proteins. Also described are methods of using these polypeptides and polynucleotides, for example for targeted cleavage of a genomic sequence.
C12N 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C07K 7/06 - Linear peptides containing only normal peptide links having 5 to 11 amino acids
75.
Regulation of gene expression using engineered nucleases
C12N 15/62 - DNA sequences coding for fusion proteins
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C12N 9/80 - Hydrolases (3.) acting on carbon to nitrogen bonds other than peptide bonds (3.5) acting on amide bonds in linear amides
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A61K 9/00 - Medicinal preparations characterised by special physical form
A method of gene editing or gene stacking within a FAD3 loci by cleaving, in a site directed manner, a location in a FAD3 gene in a cell, to generate a break in the FAD3 gene and then ligating into the break a nucleic acid molecule associated with one or more traits of interest is disclosed.
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
A61K 35/42 - Respiratory system, e.g. lungs, bronchi or lung cells
Disclosed herein are methods and compositions for inactivating MEW genes, using zinc finger nucleases (ZFNs) comprising a zinc finger protein and a cleavage domain or cleavage half-domain in conditions able to preserve cell viability. Polynucleotides encoding ZFNs, vectors comprising polynucleotides encoding ZFNs and cells comprising polynucleotides encoding ZFNs and/or cells comprising ZFNs are also provided.
C07K 16/28 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
Described herein are DNA-editing complexes, particularly DNA-editing complexes that specifically alter a single base pair in target DNA sequence as well as methods of making and using these DNA-editing complexes.
Disclosed herein are compositions comprising non-naturally occurring zinc finger domains, fusion proteins comprising these zinc finger domains, polynucleotides encoding these proteins, cells expressing these proteins and pharmaceutical compositions comprising these proteins or polynucleotides as well as methods of modifying an Htt gene using these compositions for treating or preventing Huntington's Disease.
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C12N 15/90 - Stable introduction of foreign DNA into chromosome
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
Described herein are lipid nanoparticles comprising cationic lipids and other lipids and also comprising engineered nucleases facilitate transfer of nucleic acids to cells.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
C12N 15/88 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using liposome vesicle
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
A61P 11/00 - Drugs for disorders of the respiratory system
Disclosed herein are methods and compositions for insertion of transgene sequences encoding proteins involved in clotting into the genome of a cell for treating conditions including hemophilias.
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
A01H 6/82 - Solanaceae, e.g. pepper, tobacco, potato, tomato or eggplant
C12N 15/66 - General methods for inserting a gene into a vector to form a recombinant vector using cleavage and ligationUse of non-functional linkers or adaptors, e.g. linkers containing the sequence for a restriction endonuclease
C12N 15/82 - Vectors or expression systems specially adapted for eukaryotic hosts for plant cells
90.
Zinc finger protein compositions for modulation of huntingtin (Htt)
C12N 15/11 - DNA or RNA fragmentsModified forms thereof
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
A61P 25/00 - Drugs for disorders of the nervous system
C12N 7/00 - Viruses, e.g. bacteriophagesCompositions thereofPreparation or purification thereof
Methods and compositions for gene disruption, gene editing or gene stacking within a FAD2 loci by cleaving, in a site directed manner, a location in a FAD2 gene in a soybean cell, to generate a break in the FAD2 gene and then optionally integrating into the break a nucleic acid molecule of interest is disclosed.
Disclosed herein are compositions for linking DNA binding domains and cleavage domains (or cleavage half-domains) to form non-naturally occurring nucleases. Also described are methods of making and using compositions comprising these linkers.
The present disclosure is in the field of genome engineering, particularly targeted integration of a functional SCID-related genes (e.g., IL2RG, RAG1 and/or RAG2 gene) into an IL2RG gene of a cell for provision of proteins lacking or deficient in SCID.
Described herein are engineered nucleases comprising mutations in the cleavage domain (e.g., FokI or homologue thereof) and/or DNA binding domain (zinc finger protein, TALE, single guide RNA) such that on-target specificity is increased.
Nucleases and methods of using these nucleases for inserting a sequence encoding a therapeutic protein such as an enzyme into a cell, thereby providing proteins or cell therapeutics for treatment and/or prevention of a lysosomal storage disease.
Nucleases and methods of using these nucleases for expressing a transgene from a safe harbor locus in a secretory tissue, and clones and animals derived therefrom.
Disclosed herein are compositions comprising non-naturally occurring zinc finger domains, fusion proteins comprising these zinc finger domains, polynucleotides encoding these proteins, cells expressing these proteins and pharmaceutical compositions comprising these proteins or polynucleotides as well as methods of modifying an Htt gene using these compositions for treating or preventing Huntington's Disease.
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
C07K 14/47 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans from vertebrates from mammals
C12N 15/90 - Stable introduction of foreign DNA into chromosome
98.
Regulation of gene expression using engineered nucleases
Disclosed herein are polypeptides, polynucleotides encoding, cells and organisms comprising novel DNA-binding domains, including TALE DNA-binding domains. Also disclosed are methods of using these novel DNA-binding domains for modulation of gene expression and/or genomic editing of endogenous cellular sequences.
patents
