The disclosure relates to a method of reprogramming one or more somatic cells, e.g., partially differentiated or fully/terminally differentiated somatic cells, to a less differentiated state, e.g., a pluripotent or multipotent state. In further embodiments the invention also relates to reprogrammed somatic cells produced by methods of the invention, to uses of said cells, and to methods for identifying agents useful for reprogramming somatic cells.
A01K 67/0275 - Genetically modified vertebrates, e.g. transgenic
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 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
C12N 15/877 - Techniques for producing new mammalian cloned embryos
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
2.
IMAGING-BASED POOLED GENETIC SCREENS WITH HIGHLY MULTIPLEXED PHENOTYPES
The present disclosure generally relates to certain image-based techniques for detecting nucleic acids and proteins in a sample. The methods provided include simultaneous detection of RNAs and proteins using RCA-MERFISH technology.
Disclosed herein are methods and agents for decreasing insulin resistance and metformin resistance by modulating insulin receptor condensates. Also disclosed are methods of screening for agents to decrease insulin resistance.
The present disclosure provides methods and compositions related to identifying agents that modulate macrophage function. The agents identified may be useful alone or in combination for treating and/or preventing diseases related to macrophage function (e.g., cancer) in a subject.
Disclosed are methods of altering expression of a gene with a promoter region CTCF binding site. Also disclosed are compositions and methods useful for treating a disease or condition involving over-expression or under-expression of a gene with a promoter region CTCF binding site. Further disclosed are cells and non-human animals with modified a promoter region CTCF binding site, as well as methods for screening for compounds that can modify the expression of a gene with a promoter region CTCF binding site.
C12N 15/90 - Stable introduction of foreign DNA into chromosome
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
6.
Methods And Systems For Quantifying Partitioning Of Agents In Vivo Based On Partitioning Of Agents In Vitro
Small molecule therapeutics can concentrate in distinct intracellular environments, some bounded by membranes, and others that may be formed by membrane-less biomolecular condensates. The chemical environments within biomolecular condensates have been proposed to differ from those outside these bodies, but the internal chemical environments of diverse condensates have yet to be explored. Here we use small molecule probes to demonstrate that condensates formed in vitro with the scaffold proteins of different biomolecular condensates harbor distinct chemical solvating properties. The chemical rules that govern selective partitioning in condensates, which we term condensate chemical grammar, can be ascertained by deep learning, allowing efficient prediction of the partitioning behavior of small molecules. The rules learned from in vitro condensates were adequate to predict the partitioning of small molecules into nucleolar condensates in living cells. Different biomolecular condensates harbor distinct chemical environments, that the chemical grammar of condensates can be ascertained by machine learning.
Provided herein are compositions and methods of modulating myeloid cell-mediated killing of cancer cells and modulating the activity of myeloid cell immune checkpoint inhibitors. Also provided herein are methods of screening for modulators of myeloid cell-mediated killing of cancer cells and modulators of myeloid cell immune checkpoint inhibitors.
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
The present disclosure, at least in part, relates to compositions (e.g., engineered nucleic acids and engineered proteins) and methods for increasing gene expression. The engineered proteins include RNA-binding proteins (e.g., RNA-binding proteins that comprise a Interleukin Enhancer Binding Factor 3 (ILF3) sequence, a Cas sequence, or a combination thereof). In some aspects, the disclosure provides methods of identifying engineered nucleic acids that are shorter in length than a gene of interest to induce expression of the gene of interest and also provides RNA-binding proteins for inducing gene expression.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
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, at least in part, relates to compositions (e.g., engineered nucleic acids and engineered proteins) and methods for increasing gene expression. The engineered proteins include RNA-binding proteins (e.g., RNA-binding proteins that comprise a Interleukin Enhancer Binding Factor 3 (ILF3) sequence, a Cas sequence, or a combination thereof). In some aspects, the disclosure provides methods of identifying engineered nucleic acids that are shorter in length than a gene of interest to induce expression of the gene of interest and also provides RNA-binding proteins for inducing gene 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 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
Provided herein are methods for generating genomic structural variation in plants, e.g., using a topoisomerase II inhibitor, such as etoposide. Also provided herein are combinations and kits for generating genomic structural variation in plants. The combinations and kits generally comprise a plant cell or plant tissue that is capable of being propagated, and a topoisomerase II inhibitor.
C12N 15/82 - Vectors or expression systems specially adapted for eukaryotic hosts for plant cells
A01N 43/90 - Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
Provided herein are compounds of Formulae (I) and (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. Also provided are methods, uses, and kits involving the disclosed compounds and pharmaceutical compositions thereof for treating and/or preventing a disease (e.g., a metabolic disorder (e.g., obesity, diabetes), a hypoxia related disease (e.g., a proliferative disease, inflammatory disease, neuromuscular disorder, neurodegenerative disorder, hypoxia, ischemia, oxidative stress, or a mitochondrial DNA related disorder), or a disease resulting from rhodoquinone depletion (e.g., a proliferative disease, inflammatory disease, neuromuscular disorder, metabolic disorder, or neurodegenerative disorder)) in a subject.
Provided herein are compounds of Formulae (I) and (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. Also provided are methods, uses, and kits involving the disclosed compounds and pharmaceutical compositions thereof for treating and/or preventing a disease (e.g., a metabolic disorder (e.g., obesity, diabetes), a hypoxia related disease (e.g., a proliferative disease, inflammatory disease, neuromuscular disorder, neurodegenerative disorder, hypoxia, ischemia, oxidative stress, or a mitochondrial DNA related disorder), or a disease resulting from rhodoquinone depletion (e.g., a proliferative disease, inflammatory disease, neuromuscular disorder, metabolic disorder, or neurodegenerative disorder)) in a subject.
A61K 31/136 - Amines, e.g. amantadine having aromatic rings, e.g. methadone having the amino group directly attached to the aromatic ring, e.g. benzeneamine
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
12.
Compositions and Methods for Making Epigenetic Modifications
The disclosure provides, in various embodiments, fusion proteins comprising a DNA-binding domain, a DNMT3A-binding domain, and a H3K4me0; and polynucleotides and vectors encoding one or more of the fusion proteins. The disclosure also provides, in various embodiments, gene-delivery systems, cells, compositions (e.g., pharmaceutical compositions) and kits comprising one or more of the fusion proteins polynucleotides, or vectors; methods of epigenetically modifying a genomic locus in a cell; and methods of treating a subject (e.g., a human) in need thereof.
An alternative route to moroidin-type bicyclic peptide biosynthesis is presented. Also included herein, it is reported that such moroidin-type bicyclic peptides are ribosomally synthesized and post-translationally modified peptides (RiPPs) in plants. Whereas D. moroides and C. argentea entail a previously uncharacterized DUF2775 family protein as candidate precursor peptides for moroidin biosynthesis, Japanese kerria (Kerria japonica) employs a BURP-domain protein as a precursor peptide similar to that of the recently reported lyciumin biosyntheti system. Disclosed herein are compositions and methods related to the biosynthesis of moroidin. In some embodiments of the disclosure, the moroidin peptides are synthetic. In other embodiments, the moroidin peptides are heterogenous. A skilled artisan will readily appreciate that based on the data disclosed herein that the present disclosure provides for the production of moroidins in transgenic host cells.
The disclosure provides, in various embodiments, fusion proteins comprising a DNA-binding domain, a DNMT3A-binding domain, and a H3K4me0; and polynucleotides and vectors encoding one or more of the fusion proteins. The disclosure also provides, in various embodiments, gene-delivery systems, cells, compositions (e.g., pharmaceutical compositions) and kits comprising one or more of the fusion proteins polynucleotides, or vectors; methods of epigenetically modifying a genomic locus in a cell; and methods of treating a subject (e.g., a human) in need thereof.
The invention relates to methods of modifying DNA methylation by contacting a cell with a catalytically inactive site specific nuclease fused to an effector domain having methylation or demethylation activity and one or more guide sequences.
Disclosed herein are compositions, methods, and transgenic animals for sex biasing offspring of male animals, as well as methods of screening for sex biasing agents.
Provided herein are methods for producing site specific PEG modifications to single domain antibodies (e.g., VHHs). Methods for producing site-specifically conjugated bivalent single domain antibodies (e.g., VHHs) are also provided. Methods for labeling (e.g., with a fluorophore or radionuclide) site-specifically PEGylated single domain antibodies and site-specifically conjugated bivalent single domain antibodies are also provided.
C07K 16/24 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans against cytokines, lymphokines or interferons
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 methods of modulating condensate dependent transcription of a gene by modulating condensate associated nucleic acids, including enhancer RNA and other regulatory RNA. Also disclosed are methods of screening for agents that modulate condensate dependent transcription of a gene by modulating condensate associated nucleic acids.
Disclosed are methods, compositions, proteins, nucleic acids, cells, vectors, compounds, reagents, and systems for the preparation of kavalactones, flavokavains, and kavalactone and flavokavain biosynthetic intermediates using enzymes expressed in heterologous host cells, such as microorganisms or plants, or using in vitro enzymatic reactions. This invention also provides for the expression of the enzymes by recombinant cell lines and vectors. Furthermore, the enzymes can be components of constructs such as fusion proteins. The kavalactones produced can be utilized to treat anxiety disorder, insomnia, and other psychological and neurological disorders. The flavokavains produced can be utilized to treat various cancers including colon, bladder, and breast cancers.
The present disclosure provides, in various aspects, engineered alcohol tolerant yeast and methods of producing high concentrations of biofuels and bioplastics from toxic feedstocks.
The present invention is concerned with single-domain antibodies directed against gasdermin D (GSDMD). The single-domain antibodies can be used in medical applications, preferably for preventing and/or treating an inflammatory disease or condition in a subject, and/or for determining the presence or absence of GSDMD oligomers in a sample obtained from a subject.
The disclosure provides, in various embodiments, fusion proteins comprising a DNA-binding domain, a DNMT3A-binding domain, and a H3K4me0; and polynucleotides and vectors encoding one or more of the fusion proteins. The disclosure also provides, in various embodiments, gene-delivery systems, cells, compositions (e.g., pharmaceutical compositions) and kits comprising one or more of the fusion proteins polynucleotides, or vectors; methods of epigenetically modifying a genomic locus in a cell; and methods of treating a subject (e.g., a human) in need thereof.
The invention relates to methods of modulating the expression of one or more genes in a cell by modulating the multimerization of a transcription factor and/or modulating the formation of enhancer-promoter DNA loops, and thereby modulating the expression of the one or more genes. The invention also relates to treating diseases and conditions involving aberrant gene expression by modulating the multimerization of a transcription factor and/or modulating the formation of enhancer-promoter DNA loops. The invention also relates to methods for screening for compounds that modulate expression of one or more genes in a cell.
C12N 15/67 - General methods for enhancing the 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
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
C12N 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
The invention provides methods for reprogramming somatic cells to generate multipotent or pluripotent cells. Such methods are useful for a variety of purposes, including treating or preventing a medical condition in an individual. The invention further provides methods for identifying an agent that reprograms somatic cells to a less differentiated state.
A01K 67/0275 - Genetically modified vertebrates, e.g. transgenic
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 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
C12N 15/877 - Techniques for producing new mammalian cloned embryos
26.
CHROMOSOME NEIGHBORHOOD STRUCTURES AND METHODS RELATING THERETO
Work described herein reveals 3D regulatory landscapes of hESCs representative of early human development. This work also demonstrates that cohesin-associated CTCF loops, and the cohesin-associate enhancer-promoter loops within them, dominate the organization of TADs. The CTCF-CTCF loops form a chromosomal scaffold of insulated neighborhoods that are largely preserved in vertebrates, and enhancer-promoter interactions occur within these neighborhoods. Genes are regulated in the context of conserved insulated neighborhood structures. Loss of neighborhood structures occurs frequently in cancer cells, and proto-oncogenes can be activated by genetic alterations that disrupt specific 3D chromosome structures.
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
G16B 20/20 - Allele or variant detection, e.g. single nucleotide polymorphism [SNP] detection
Disclosed are methods of altering expression of a gene with a promoter region CTCF binding site. Also disclosed are compositions and methods useful for treating a disease or condition involving over-expression or under-expression of a gene with a promoter region CTCF binding site. Further disclosed are cells and non-human animals with modified a promoter region CTCF binding site, as well as methods for screening for compounds that can modify the expression of a gene with a promoter region CTCF binding site.
C12N 15/90 - Stable introduction of foreign DNA into chromosome
C12Q 1/6886 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
The present disclosure relates to pharmaceutical compositions comprising engineered macrophages and methods of use thereof. In some aspects, the present disclosure relates to engineered macrophages derived from pluripotent stem cells. In some embodiments, the stem cell genome is edited to knock-out (e g., SIRPa) and/or knock-in (e g., CAR) genes of interest prior to differentiation into macrophages. In some embodiments, engineered macrophages lack a SIRPa receptor. In some embodiments, the engineered macrophages express chimeric antigen receptors that induce and/or enhance phagocytosis. Alternatively, or additionally, in some embodiments, macrophages are engineered with combinatorial antigen-sensing circuits to improve tumor recognition and phagocytosis. Other aspects of the disclosure relate to methods of treating cancer in a subject and/or methods of enhancing cancer cell phagocytosis.
Modified tRNAs can be used to express in a mammalian cell a functional gene product encoded by a gene containing a premature stop codon and/or to treat a disease mediated by a premature stop codon.
The present disclosure relates to the discovery that IFN-ω activates macrophages to target cancer cells and can therefore be used as a therapeutic strategy for increasing macrophage-mediated cancer cytotoxicity in a subject. In one aspect, the present disclosure provides methods of treating a proliferative disease (e.g., cancer) in a subject in need thereof comprising administering to the subject a therapeutically effective amount of interferon-omega (IFN-ω) or an analog thereof, or an agent that increases endogenous interferon-omega (IFN-ω) expression in the subject.
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
The present disclosure provides methods and compositions related to the combination therapy of a macrophage-directed immunotherapy and a cytokine (e.g., IL-10). The combination of the macrophage-directed immunotherapy and a cytokine is useful in treating and/or preventing cancer (e.g., lung cancer) in a subject. Therapies that activate macrophages are emerging in cancer immunotherapy. One potential therapeutic target is the CD47-SIRPa, interaction, which acts as a myeloid immune checkpoint. Cluster of Differentiation 47 (CD47) is highly expressed on many different types of cancer cells, including lung cancer cells. CD47 binds to an inhibitory receptor, signal regulatory protein alpha (SIRPa,), that is expressed on the surface of macrophages and other myeloid immune cells.
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
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 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
32.
COMPOSITIONS AND METHODS FOR MAMMALIAN GENETICS AND USES THEREOF
The invention provides compositions and methods for performing mammalian cell genetics, e.g., genetic screens, using near-haploid cells. The invention further provides genes and gene products isolated using the inventive methods and methods of use thereof.
Methods of reducing viability of a parasite in a subject involve administering an effective amount of an inhibitor of guanosine-5'-triphosphate cyclohydrolase I (GCH) to the subject. Methods of identifying an agent that reduces viability of an apicomplexan parasite involve culturing an apicomplexan parasite in a cell culture; adding an agent to the cell culture; and detecting a concentration of one or more of 7,8-dihydroneopterin triphosphate, 6-pyruvoyl-tetrahydropterin, tetrahydrobiopterin, tetrahydrofolate, folate, dihydrofolate, or dihydrobiopterin in the cell culture after a period of time.
Methods for developing disease-related nanobodies and related products and kits are provided. The disease-specific proteins are extracellular matrix (ECM) proteins, domains or epitopes that are associated with various aspects of disease and are not present, or are present in very low quantities, in non-diseased individuals. Highly effective nanobodies capable of specifically binding to these ECM protein epitopes useful in in vivo imaging assays, the detection, diagnosis and treatment of diseases as well as monitoring therapeutic progress in a patient with a disease are provided herein.
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
A61P 35/04 - Antineoplastic agents specific for metastasis
A61K 49/08 - Nuclear magnetic resonance [NMR] contrast preparationsMagnetic resonance imaging [MRI] contrast preparations characterised by the carrier
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61K 51/10 - Antibodies or immunoglobulinsFragments thereof
C07K 14/78 - Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin or cold insoluble globulin [CIG]
C07K 16/18 - Immunoglobulins, e.g. monoclonal or polyclonal antibodies against material from animals or humans
Small molecule therapeutics can concentrate in distinct intracellular environments, some bounded by membranes, and others that may be formed by membrane-less biomolecular condensates. The chemical environments within biomolecular condensates have been proposed to differ from those outside these bodies, but the internal chemical environments of diverse condensates have yet to be explored. Here we use small molecule probes to demonstrate that condensates formed in vitro with the scaffold proteins of different biomolecular condensates harbor distinct chemical solvating properties. The chemical rules that govern selective partitioning in condensates, which we term condensate chemical grammar, can be ascertained by deep learning, allowing efficient prediction of the partitioning behavior of small molecules. The rules learned from in vitro condensates were adequate to predict the partitioning of small molecules into nucleolar condensates in living cells. Different biomolecular condensates harbor distinct chemical environments, that the chemical grammar of condensates can be ascertained by machine learning.
G16B 40/00 - ICT specially adapted for biostatisticsICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
G16B 35/00 - ICT specially adapted for in silico combinatorial libraries of nucleic acids, proteins or peptides
G16C 20/00 - Chemoinformatics, i.e. ICT specially adapted for the handling of physicochemical or structural data of chemical particles, elements, compounds or mixtures
G16H 70/60 - ICT specially adapted for the handling or processing of medical references relating to pathologies
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data miningICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
Expression of a target gene is modulated by an agent that modulates binding between a selected ribonucleic acid (RNA) transcribed from at least one regulatory element of a target gene and a transcription factor that binds to both the RNA and the at least one regulatory element. The agent is selected to bind to an RNA having binding affinity for a region of the transcription factor that is at least nine contiguous amino acids, at least one amino acid of the region is arginine, and a majority of amino acids of the region are arginine or lysine. Modulating binding between the RNA and the transcription factor modulates expression of the target gene.
The present disclosure provides methods and compositions related to identifying agents that modulate macrophage function. The agents identified may be useful alone or in combination for treating and/or preventing diseases related to macrophage function (e.g., cancer) in a subject.
The present disclosure provides methods and compositions related to the combination therapy of a macrophage-directed immunotherapy and a targeted agent. The combination of the macrophage-directed immunotherapy and a targeted agent is useful in treating and/or preventing cancer (e.g., lung cancer) in a subject.
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
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
39.
CDC20 VARIANTS RESISTANT TO ANTI-MITOTIC DRUGS AND RELATED METHODS AND COMPOSITIONS
Disclosed are methods of screening for agents to treat cancers resistant to anti-mitotic therapy, methods of detecting cancers resistant to anti-mitotic therapy, and methods of treating cancers resistant to anti-mitotic therapy.
The invention provides compositions and methods of use in reprogramming somatic cells. Compositions and methods of the invention are of use, e.g., for generating or modulating (e.g., enhancing) generation of induced pluripotent stem cells by reprogramming somatic cells. The reprogrammed somatic cells are useful for a number of purposes, including treating or preventing a medical condition in an individual. The invention further provides methods for identifying an agent that reprograms somatic cells to a pluripotent state and/or enhances the speed and/or efficiency of reprogramming. Certain of the compositions and methods relate to modulating the Wnt pathway.
Provided herein are compositions and methods of modulating myeloid cell-mediated killing of cancer cells and modulating the activity of myeloid cell immune checkpoint inhibitors. Also provided herein are methods of screening for modulators of myeloid cell-mediated killing of cancer cells and modulators of myeloid cell immune checkpoint inhibitors.
Provided herein are methods of screening for agents that can partition in viral condensates and therefore may be effective anti-viral agents. Also disclosed are methods of optimizing the activity and reducing the side effects of known or suspected anti-viral agents by screening the portioning of modified known or suspected anti-viral agents in viral condensates and other condensates occurring in cells (e.g., transcriptional condensates).
An alternative route to moroidin-type bicyclic peptide biosynthesis is presented. Also included herein, it is reported that such moroidin-type bicyclic peptides are ribosomally synthesized and post-translationally modified peptides (RiPPs) in plants. Whereas D. moroides and C. argentea entail a previously uncharacterized DUF2775 family protein as candidate precursor peptides for moroidin biosynthesis, Japanese kerria (Kerriajaponica) employs a BURP-domain protein as a precursor peptide similar to that of the recently reported lyciumin biosyntheti system. Disclosed herein are compositions and methods related to the biosynthesis of moroidin. In some embodiments of the disclosure, the moroidin peptides are synthetic. In other embodiments, the moroidin peptides are heterogenous. A skilled artisan will readily appreciate that based on the data disclosed herein that the present disclosure provides for the production of moroidins in transgenic host cells.
Provided herein are compounds of Formulae (I) and (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. Also provided are methods, uses, and kits involving the disclosed compounds and pharmaceutical compositions thereof for treating and/or preventing a disease (e.g., a metabolic disorder (e.g., obesity, diabetes), a hypoxia related disease (e.g., a proliferative disease, inflammatory disease, neuromuscular disorder, neurodegenerative disorder, hypoxia, ischemia, oxidative stress, or a mitochondrial DNA related disorder), or a disease resulting from rhodoquinone depletion (e.g., a proliferative disease, inflammatory disease, neuromuscular disorder, metabolic disorder, or neurodegenerative disorder)) in a subject.
C07C 211/44 - Compounds containing amino groups bound to a carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having amino groups bound to only one six-membered aromatic ring
Disclosed herein are methods and compositions for modulating MFSD12 expression and activity to treat diseases such as lysosomal storage diseases, including cystinosis. Also disclosed are methods of altering skin pigmentation and methods of screening for MFSD12 modulation agents.
The invention relates to methods of modifying DNA methylation by contacting a cell with a catalytically inactive site specific nuclease fused to an effector domain having methylation or demethylation activity and one or more guide sequences.
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
A61P 9/00 - Drugs for disorders of the cardiovascular system
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Disclosed herein are compositions and methods for labeling cells using click chemistry reagents. The compositions and methods disclosed herein provide a specific and efficient means of localizing desired agents to a variety of cell types in vivo and in vitro. The compositions and methods disclosed herein can be used to deliver a variety of desired agents to a cell or population of cells to direct cell fate and/or cell differentiation.
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
C12N 15/11 - DNA or RNA fragmentsModified forms thereof
Aspects of the present disclosure provide compositions comprising NEK10 for example, wild-type NEK10 or a hyper-active NEK10 mutant such as NEK10S684D, and methods of using such for treating a respiratory disorder such as bronchiectasis.
Transgenic host cells, vectors useful for making transgenic host cells, and kits useful for making transgenic host cells are described. Also described are transgenic plants. In some embodiments, transgenic host cells express a 4-hydroxyphenylacetaldehyde synthase (4HPAAS). In some embodiments, transgenic host cells express a tyrosol:UDP-glucose 8-O-glucosyltransferase (T8GT). The transgenic host cells are useful for biosynthesis of one or more of salidroside, icariside D2, tyrosol, and 4-hydroxypenylacetaldehyde.
In some aspects, described herein are cell culture media that are useful for in vitro culture of mammalian cells. The culture media contain a variety of small organic compounds that are found in normal adult human blood. Also described are methods of using the culture media for a variety of purposes. Also described are methods of treating cancer.
Disclosed herein are methods and agents for decreasing insulin resistance and metformin resistance by modulating insulin receptor condensates. Also disclosed are methods of screening for agents to decrease insulin resistance.
The disclosure relates to covalent protein dimers of MYC, MAX, and Omomyc; pharmaceutical compositions comprising the covalent protein dimers; methods of making the covalent protein dimers; and methods of treating disorders associated with MYC dysregulation (e.g., cancer) with the covalent protein dimers.
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
53.
METHODS AND COMPOSITIONS FOR EFFICIENT PRODUCTION OF BIOFUELS AND BIOPLASTICS FROM TOXIC FEEDSTOCKS
The present disclosure provides, in various aspects, engineered alcohol tolerant yeast and methods of producing high concentrations of biofuels and bioplastics from toxic feedstocks.
Described herein are methods of characterizing agent incorporation into condensates, methods of reducing transcription of oncogenes associated with condensates, and methods of using peptides to inhibit nuclear receptor and cofactor binding in condensates.
Potassium chloride cotransporter-2 (KCC2) plays a critical role in brain function, and deficiency in KCC2 has been linked to neurological diseases, psychiatric disorders, and central nervous system injuries. In particular, Rett syndrome (RTT), a severe neurodevelopmental disorder caused by mutations in the X-linked gene Methyl CpG binding Protein 2 (MECP2), has been linked to deficits in KCC2. The disclosure reports the use of CRISPR/Cas9 genome-editing technology to generate stem cell-derived, genetically defined KCC2 reporter human neurons for large-scale compound screening. This screening platform has been utilized to identify a number of small molecule compounds that are capable of enhancing KCC2 expression in both wild-type and RTT neurons, as well as organotypical brain slices cultured from wild-type mice. These first-in class compounds may be applied as a novel therapeutic approach to restore the impaired balance between excitation and inhibition observed in neurological diseases, psychiatric disorders, and central nervous system injuries.
A61K 31/4525 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
A61K 31/4709 - Non-condensed quinolines containing further heterocyclic rings
A61K 31/519 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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
56.
ENHANCED METHODS FOR INDUCING AND MAINTAINING NAIVE HUMAN PLURIPOTENT STEM CELLS
The present disclosure provides methods and compositions for inducing, maintaining and/or passaging naïve pluripotent stem cell. In some embodiments, the methods are performed in the absence of MEK inhibition which has been shown to result in genomic instability of naïve pluripotent stem cells.
The invention provides compositions and methods of use in reprogramming somatic cells. Compositions and methods of the invention are of use, e.g., for generating or modulating (e.g., enhancing) generation of induced pluripotent stem cells by reprogramming somatic cells. The reprogrammed somatic cells are useful for a number of purposes, including treating or preventing a medical condition in an individual. The invention further provides methods for identifying an agent that reprograms somatic cells to a pluripotent state and/or enhances the speed and/or efficiency of reprogramming. Certain of the compositions and methods relate to modulating the Wnt pathway.
C12N 15/00 - Mutation or genetic engineeringDNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purificationUse of hosts therefor
Disclosed herein are methods and compositions for modulating MCART1 expression and activity to treat diseases such as cancer and age related conditions. Also disclosed are methods of screening for MCART1 modulation agents.
The present disclosure provides genetically altered protozoan parasites comprising a mutation in a bradyzoite formation deficient 1 (BFD1) gene, wherein the mutation inhibits differentiation of the parasite into a bradyzoite. The genetically altered protozoan parasites can be utilized in vaccine compositions and in methods of treating apicomplexan parasite infection.
Disclosed herein are methods of modulating condensate dependent transcription of a gene by modulating condensate associated nucleic acids, including enhancer RNA and other regulatory RNA. Also disclosed are methods of screening for agents that modulate condensate dependent transcription of a gene by modulating condensate associated nucleic acids.
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
A61K 31/711 - Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
C12Q 1/6811 - Selection methods for production or design of target specific oligonucleotides or binding molecules
62.
METHODS AND ASSAYS FOR MODULATING GENE TRANSCRIPTION BY MODULATING CONDENSATES
Described herein are compositions and methods for modulating gene regulation by modulating condensate formation, composition, maintenance, dissolution and regulation.
A tRNA that hybridizes to a non-optimal codon can be used to increase expression in a mammalian cell of a gene product encoded by a gene containing the non-optimal codon or to treat a haploinsufficiency disorder in a subject having a haploinsufficient gene containing the non-optimal codon.
Disclosed are methods, compositions, proteins, nucleic acids, cells, vectors, compounds, reagents, and systems for the preparation of kavalactones, flavokavains, and kavalactone and flavokavain biosynthetic intermediates using enzymes expressed in heterologous host cells, such as microorganisms or plants, or using in vitro enzymatic reactions. This invention also provides for the expression of the enzymes by recombinant cell lines and vectors. Furthermore, the enzymes can be components of constructs such as fusion proteins. The kavalactones produced can be utilized to treat anxiety disorder, insomnia, and other psychological and neurological disorders. The flavokavains produced can be utilized to treat various cancers including colon, bladder, and breast cancers.
Disclosed are methods, compositions, proteins, nucleic acids, cells, vectors, compounds, reagents, and systems for the preparation of kavalactones, flavokavains, and kavalactone and flavokavain biosynthetic intermediates using enzymes expressed in heterologous host cells, such as microorganisms or plants, or using in vitro enzymatic reactions. This invention also provides for the expression of the enzymes by recombinant cell lines and vectors. Furthermore, the enzymes can be components of constructs such as fusion proteins. The kavalactones produced can be utilized to treat anxiety disorder, insomnia, and other psychological and neurological disorders. The flavokavains produced can be utilized to treat various cancers including colon, bladder, and breast cancers.
Provided herein are methods of screening for agents that can partition in viral condensates and therefore may be effective anti-viral agents. Also disclosed are methods of optimizing the activity and reducing the side effects of known or suspected anti-viral agents by screening the portioning of modified known or suspected anti-viral agents in viral condensates and other condensates occurring in cells (e.g., transcriptional condensates).
The invention relates to methods of using choline supplementation for treating APOE4-related disorders. In particular the methods are accomplished by administering choline treatment paradigms to re-establish lipid homeostasis in APOE4 carriers.
A61K 31/14 - Quaternary ammonium compounds, e.g. edrophonium, choline
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 invention relates to methods of using choline supplementation for treating APOE4-related disorders. In particular the methods are accomplished by administering choline treatment paradigms to re-establish lipid homeostasis in APOE4 carriers.
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
69.
COMPOSITIONS AND METHODS FOR MODIFIED DENDRIMER NANOPARTICLE DELIVERY
Compositions and methods for modified dendrimer nanoparticle (“MDNP”) delivery of therapeutic, prophylactic and/or diagnostic agent such as large repRNA molecules to the cells of a subject have been developed. MDNPs efficiently drive proliferation of antigen-specific T cells against intracellular antigen, and potentiate antigen-specific antibody responses. MDNPs can be multiplexed to deliver two or more different repRNAs to modify expression kinetics of encoded antigens and to simultaneous deliver repRNAs and mRNAs including the same UTR elements that promote expression of encoded antigens.
A61K 9/00 - Medicinal preparations characterised by special physical form
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
A61K 39/145 - Orthomyxoviridae, e.g. influenza virus
Provided herein are analogs of the natural product icariin represented by Structural Formula (I) or a pharmaceutically acceptable salt thereof. The analogs can be used to modulate (e.g., inhibit, such as by competitive inhibition) PDE5 and thereby treat a wide range of PDE5-mediated diseases, including cardiovascular, gastrointestinal, pulmonary, musculoskeletal, neurological and reproductive diseases. Also provided herein are compositions and methods including compounds of Structural Formula (I).
C07H 15/26 - Acyclic or carbocyclic radicals, substituted by hetero rings
C07D 311/28 - Benzo [b] pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only
71.
Methods and compositions for treating a premature stop codon-mediated disorder
Modified tRNAs can be used to express in a mammalian cell a functional gene product encoded by a gene containing a premature stop codon and/or to treat a disease mediated by a premature stop codon.
In some aspects, the disclosure provides methods for modulating mitochondrial transport of serine in a cell, the methods comprising modulating expression or activity of one or more sideroflexins. In some aspects, methods of identifying agents that modulate sideroflexin expression or activity are provided. In some aspects, methods of treating cancer are provided.
C07H 21/04 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
A61K 31/713 - Double-stranded nucleic acids or oligonucleotides
G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
Disclosed herein are methods useful for modulating expression of a target gene by modulating binding between a ribonucleic acid (RNA) transcribed from at least one regulatory element of a target gene and a transcription factor which binds to both the RNA and the regulatory element. Also disclosed herein are methods and assays for identifying agents that interfere with binding between RNA transcribed from at least one regulatory element and a transcription factor which binds to the RNA and to the regulatory element.
Disclosed herein are compositions and methods for labeling cells using click chemistry reagents. The compositions and methods disclosed herein provide a specific and efficient means of localizing desired agents to a variety of cell types in vivo and in vitro. The compositions and methods disclosed herein can be used to deliver a variety of desired agents to a cell or population of cells to direct cell fate and/or cell differentiation.
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 9/127 - Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
A61K 31/655 - Azo (—N=N—), diazo (=N2), azoxy (N—O—N or N(=O)—N), azido (—N3) or diazoamino (—N=N—N) compounds
A61K 31/704 - Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin, digitoxin
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
The present disclosure provides compounds of any one of Formulae (A) to (L). The present disclosure also provides compositions, uses, and methods that include or involve a compound described herein, a serine/threonine-protein kinase B-Raf (BRAF) inhibitor, an epidermal growth factor receptor (EGFR) inhibitor, a vascular endothelial growth factor 1 (VEGFR1) inhibitor, a fibroblast growth factor receptor 1 (FGFR1) inhibitor, or a combination thereof. The compounds, compositions, uses, and methods are useful in changing the pluripotency state of a vertebrate cell to a more naïve state.
Aspects of the present disclosure provide compositions comprising NEK10 for example, wild-type NEK10 or a hyperactive NEK10 mutant such as NEK10S684D, and methods of using such for treating a respiratory disorder such as bronchiectasis.
Disclosed herein are methods and compositions for modulating MFSD12 expression and activity to treat diseases such as lysosomal storage diseases, including cystinosis. Also disclosed are methods of altering skin pigmentation and methods of screening for MFSD12 modulation agents.
The invention provides a method for isolating particular members from a library of variant cells in individual microreactors, wherein the phenotype of the biomolecule secreted by the cell is evaluated on the basis of multiple parameters, including substrate specificity and kinetic efficiency.
Presidents and Fellows of Harvard University (USA)
Massachusetts Institute of Technology (USA)
Whitehead Institute for Biomedical Research (USA)
University of Massachusetts (USA)
Inventor
Dekker, Job
Aiden, Erez Lieberman
Van Berkum, Nynke
Gnirke, Andreas
Lander, Eric
Nusbaum, Chad
Williams, Louise
Melnikov, Alexandre
Giannoukos, Georgia
Abstract
The disclosed Hi-C protocol can identify genomic loci that are spatially co-located in vivo. These spatial co-locations may include, but are not limited to, intrachromosomal interactions and/or interchromosomal interactions. Hi-C techniques may be applied to many different scales of interest. For example, on a large scale, Hi-C techniques can be used to identify long-range interactions between distant genomic loci.
C12Q 1/6837 - Enzymatic or biochemical coupling of nucleic acids to a solid phase using probe arrays or probe chips
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving nucleic acids
C07H 21/04 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
The present invention, in some aspects, provides methods, reagents, compositions, and kits for the radiolabeling of proteins, for example, of proteins useful for positron emission tomography (PET) or single-photon emission computed tomography (SPECT) (e.g., for diagnostic and therapeutic applications), using sortase-mediated transpeptidation reactions. Some aspects of this invention provide methods for the conjugation of an agent, for example, a radioactive agent or molecule to diagnostic or therapeutic peptides or proteins. Compositions comprising sortagged, radiolabeled proteins as well as reagents for generating radiolabeled proteins are also provided. Kits comprising reagents useful for the generation of radiolabeled proteins are provided, as are precursor proteins that comprise a sortase recognition motif.
C07H 5/02 - Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium to halogen
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
83.
COMPOSITIONS AND METHODS FOR REGULATION OF CHRONIC TOXOPLASMA INFECTION
BFD1 BFD1 ) gene, wherein the mutation inhibits differentiation of the parasite into a bradyzoite. The genetically altered protozoan parasites can be utilized in vaccine compositions and in methods of treating apicomplexan parasite infection.
Described herein are methods of characterizing agent incorporation into condensates, methods of reducing transcription of oncogenes associated with condensates, and methods of using peptides to inhibit nuclear receptor and cofactor binding in condensates.
Described herein are methods of characterizing agent incorporation into condensates, methods of reducing transcription of oncogenes associated with condensates, and methods of using peptides to inhibit nuclear receptor and cofactor binding in condensates.
Lyciumin cyclic peptides and methods of producing lyciumin cyclic peptides are described. A host cell can include a transgene encoding a lyciumin precursor peptide, or a biologically-active fragment thereof. The lyciumin precursor peptide, or biologically-active fragment thereof, can include one or more core lyciumin peptide domains. The transgene can be expressed in the host cell to thereby produce a lyciumin precursor peptide, or biologically-active fragment thereof. The lyciumin precursor peptide, or biologically-active fragment thereof, can be converted to one or more lyciumin cyclic peptides in the host cell. A library of nucleic acids encoding lyciumin precursor peptides, or biologically-active fragments thereof, can be generated.
Disclosed herein are methods and compositions for modulating MCART1 expression and activity to treat diseases such as cancer and age related conditions. Also disclosed are methods of screening for MCART1 modulation agents.
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61P 11/00 - Drugs for disorders of the respiratory system
A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agentsNon-steroidal antiinflammatory drugs [NSAID]
Disclosed are methods, systems, cells and compositions directed to modeling a physiologic or pathologic process in an animal using a set of yeast genes analogous to a set of animal genes and augmenting the physiologic or pathologic process in the animal with predicted gene interactions based on the interactions between the set of yeast genes. Also disclosed are methods of screening for and using therapeutics for neurodegenerative proteinopathies.
G01N 33/48 - Biological material, e.g. blood, urineHaemocytometers
C12Q 1/02 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving viable microorganisms
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
G16B 5/00 - ICT specially adapted for modelling or simulations in systems biology, e.g. gene-regulatory networks, protein interaction networks or metabolic networks
G16B 25/00 - ICT specially adapted for hybridisationICT specially adapted for gene or protein expression
The invention provides methods for reprogramming somatic cells to generate multipotent or pluripotent cells. Such methods are useful for a variety of purposes, including treating or preventing a medical condition in an individual. The invention further provides methods for identifying an agent that reprograms somatic cells to a less differentiated state.
A01K 67/0275 - Genetically modified vertebrates, e.g. transgenic
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 15/877 - Techniques for producing new mammalian cloned embryos
90.
METHODS AND SYSTEMS FOR RECONSTRUCTION OF DEVELOPMENTAL LANDSCAPES BY OPTIMAL TRANSPORT ANALYSIS
Methods and compositions for producing induced pluripotent stem cell by introducing nucleic acids encoding one or more transcription factors including Obox6 into a target cell.
Modified tRNAs can be used to express in a mammalian cell a functional gene product encoded by a gene containing a premature stop codon and/or to treat a disease mediated by a premature stop codon.
A61K 31/34 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
A61K 47/34 - Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
92.
METHODS AND COMPOSITIONS FOR INCREASING PROTEIN EXPRESSION AND/OR TREATING A HAPLOINSUFFICIENCY DISORDER
A tRNA that hybridizes to a non-optimal codon can be used to increase expression in a mammalian cell of a gene product encoded by a gene containing the non-optimal codon or to treat a haploinsufficiency disorder in a subject having a haploinsufficient gene containing the non-optimal codon.
A tRNA that hybridizes to a non-optimal codon can be used to increase expression in a mammalian cell of a gene product encoded by a gene containing the non-optimal codon or to treat a haploinsufficiency disorder in a subject having a haploinsufficient gene containing the non-optimal codon.
Modified tRNAs can be used to express in a mammalian cell a functional gene product encoded by a gene containing a premature stop codon and/or to treat a disease mediated by a premature stop codon.
A61K 47/18 - AminesAmidesUreasQuaternary ammonium compoundsAmino acidsOligopeptides having up to five amino acids
A61K 47/20 - Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
A61K 47/34 - Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 31/34 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
95.
KCC2 expression enhancing compounds and uses thereof
Potassium chloride cotransporter-2 (KCC2) plays a critical role in brain function, and deficiency in KCC2 has been linked to neurological diseases, psychiatric disorders, and central nervous system injuries. In particular, Rett syndrome (RTT), a severe neurodevelopmental disorder caused by mutations in the X-linked gene Methyl CpG binding Protein 2 (MECP2), has been linked to deficits in KCC2. The disclosure reports the use of CRISPR/Cas9 genome-editing technology to generate stem cell-derived, genetically defined KCC2 reporter human neurons for large-scale compound screening. This screening platform has been utilized to identify a number of small molecule compounds that are capable of enhancing KCC2 expression in both wild-type and RTT neurons, as well as organotypical brain slices cultured from wild-type mice. These first-in class compounds may be applied as a novel therapeutic approach to restore the impaired balance between excitation and inhibition observed in neurological diseases, psychiatric disorders, and central nervous system injuries.
A61K 31/496 - Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
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 31/4525 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
Methods for the in vitro production of enucleated red blood cells and the enucleated red blood cells thus prepared are provided. Such enucleated red blood cells may express a sortaggable surface protein, which allows for surface modification in the presence of a sortase. Also described herein are surface modified enucleated red blood cells, e.g., conjugated with an agent of interest such as a peptide, a detectable label, or a chemotherapeutic agent, and uses thereof in delivering the agent to a subject.
A01K 67/0275 - Genetically modified vertebrates, e.g. transgenic
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
Provided herein are analogs of the natural product icariin represented by Structural Formula (I) or a pharmaceutically acceptable salt thereof. The analogs can be used to modulate (e.g., inhibit, such as by competitive inhibition) PDE5 and thereby treat a wide range of PDE5- mediated diseases, including cardiovascular, gastrointestinal, pulmonary, musculoskeletal, neurological and reproductive diseases. Also provided herein are compositions and methods including compounds of Structural Formula (I).
A01N 43/16 - Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one or more oxygen or sulfur atoms as the only ring hetero atom with one hetero atom six-membered rings with oxygen as the ring hetero atom
A61K 31/35 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
A61K 31/353 - 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
98.
Nucleic acid constructs encoding reprogramming factors linked by self-cleaving peptides
The disclosure relates to a method of reprogramming one or more somatic cells, e.g., partially differentiated or fully/terminally differentiated somatic cells, to a less differentiated state, e.g., a pluripotent or multipotent state. In further embodiments the invention also relates to reprogrammed somatic cells produced by methods of the invention, to chimeric animals comprising reprogrammed somatic cells of the invention, to uses of said cells, and to methods for identifying agents useful for reprogramming somatic cells.
G01N 33/50 - Chemical analysis of biological material, e.g. blood, urineTesting involving biospecific ligand binding methodsImmunological testing
A01K 67/027 - New or modified breeds of vertebrates
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 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
The invention provides compositions and methods for performing mammalian cell genetics, e.g., genetic screens, using near-haploid cells. The invention further provides genes and gene products isolated using the inventive methods and methods of use thereof.
It has been established that exposure to cytotoxic doses of HSP90 inhibitor is broadly immunosuppressive, whereas continuous exposure to low-dosages of the same inhibitor exerts anti-tumor activity. The anti-tumor activity is mediated by the host immune system. Compositions and methods for continuous, low-dose exposure to HSP90 inhibitors in combination with one or more immunostimulatory agents for the treatment of cancer are described. Typically, the HSP90 inhibitor is administered in an amount that is between 1% and 20% of the clinically-determined maximum tolerate dose. The immunostimulatory agent can be administered simultaneously with the HSP90 inhibitor, or at some time before or after the HSP90 inhibitor. Compositions including a sub-toxic dose of HSP90 inhibitor in combination with an immunostimulatory agent in an amount effective to treat cancer are also provided.
patents
