Provided herein are compounds and compositions useful in increasing PPARδ activity. The compounds and compositions provided herein are useful for the treatment of PPARδ related diseases (e.g., muscular diseases, vascular disease, demyelinating disease, and metabolic diseases).
C07D 401/04 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
A61P 21/00 - Drugs for disorders of the muscular or neuromuscular system
A61P 25/00 - Drugs for disorders of the nervous system
C07D 233/64 - Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
C07D 405/10 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing aromatic rings
Disclosed herein are homology-independent targeted integration methods of integrating an exogenous DNA sequence into a genome of a cell and compositions for such methods. Methods herein comprise contacting the cell with a composition comprising a targeting construct comprising the exogenous DNA sequence and a targeting sequence, a complementary strand oligonucleotide homologous to the targeting sequence, and a nuclease, thereby altering the genome of the cell.
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 diseases; Gene 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
Electro-optical microprobes and methods for forming and using the electro-optical microprobes are disclosed. In one aspect, an electro-optical microprobe includes an optical waveguide including first and second ends and a side surface between the first and the second ends, a first layer including a first electrically conductive material disposed over the side surface of the optical waveguide, a second layer including an electrically conductive polymer disposed on a portion of the first layer proximate to the first end of the optical waveguide, and an isolation layer including an electrically insulative material disposed the second layer and a remaining portion of the first layer that is not covered by the second layer.
G02F 1/29 - Devices or arrangements for the control of the intensity, colour, phase, polarisation or direction of light arriving from an independent light source, e.g. switching, gating or modulating; Non-linear optics for the control of the position or the direction of light beams, i.e. deflection
The present disclosure provides compositions and methods for increasing suberin production in plants, for example by increasing MYB41 expression in a plant. In some examples, MYB41 expression is by a heterologous promoter, such as a FACT gene promoter, a HORST gene promoter, a GPAT5 gene promoter, a RALPH gene promoter, a ASFT gene promoter, or a MYB84 gene promoter.
7.
SELECTIVE CELL TARGETING USING ADENOVIRUS AND CHEMICAL DIMERS
Compositions and methods for retargeting adenovirus to a cell using chemical dimers are described. In particular, a recombinant adenovirus comprising a nucleic acid comprising a capsid-dimerizing agent binder conjugate and a ligand-dimerizing agent binder conjugate is provided.
Bacillus anthracisStaphylococcus aureusStaphylococcus aureusStaphylococcus aureus (MRSA), or has been exposed to an organophosphate (OP). Such methods include determining the measuring methylation status of numerous differentially methylated regions (DMRs) in the genomic DNA of particular PBMCs, such as those provided in Table 1, and in some examples also determining an amount of accessible chromatin in the isolated immune cells. Also provided are nucleic acid probes, arrays, solid supports (such a chip or nanosphere) and kits that can be used with such methods.
Provided are methods of treating a neurodegenerative disease or condition in a subject in need thereof including administering a cannabinoid to the subject.
A61K 31/00 - Medicinal preparations containing organic active ingredients
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
10.
NON-INVASIVE CELLULAR STIMULATION WITH UNIFORM ULTRASOUND FIELDS AND PREDICTION OF NEURONAL ACTIVITY RESULTING THEREFROM
A system of ultrasound based cellular stimulation may include a stimulation apparatus and a stimulation controller. The stimulation apparatus may include a transducer element formed from a single crystal piezoelectric material such as lithium niobate. The stimulation apparatus may deliver high magnitudes of acoustic pressure relative to its dimensions (e.g., size, weight, and/or the like) and without significant heating. The stimulation controller may determine a cellular response to ultrasound stimulation such as membrane deflection and transmembrane voltage change. The stimulation controller may determine, based on the predicted cellular response, parameters for an ultrasound stimulation treatment for a patient such as a magnitude and/or duration of an ultrasonic stimulus for achieving a desired magnitude of membrane deflection and/or transmembrane voltage changes. The ultrasound stimulation treatment may be administered to the patient by the stimulation apparatus operating in accordance with the parameters.
B06B 1/06 - Processes or apparatus for generating mechanical vibrations of infrasonic, sonic or ultrasonic frequency making use of electrical energy operating with piezoelectric effect or with electrostriction
G16B 5/00 - ICT specially adapted for modelling or simulations in systems biology, e.g. gene-regulatory networks, protein interaction networks or metabolic networks
G16H 20/30 - ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to physical therapies or activities, e.g. physiotherapy, acupressure or exercising
G16H 40/67 - ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices for the operation of medical equipment or devices for remote operation
11.
SYNTHETIC ANALOGS OF CANNABINOL (CBN) FOR THE TREATMENT OF AGE-RELATED NEUROLOGICAL DISORDERS
Disclosed herein are compounds having a structure according to Formula I Formula I. Also disclosed are methods for making and using the compounds. The compounds may be useful for treating or preventing a disease or condition in a subject, including a neurodegenerative disease or condition, a metabolic disorder, a traumatic brain injury, or cancer.
C07D 311/58 - Benzo [b] pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulfur atoms in position 2 or 4
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 31/00 - Medicinal preparations containing organic active ingredients
A61K 31/353 - 3,4-Dihydrobenzopyrans, e.g. chroman, catechin
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
12.
METHODS AND COMPOSITIONS FOR EXPRESSION OF EDITING PROTEINS
Provided herein are compositions and systems for reconstitution of RNA molecules, including methods for using these molecules. For example, such molecules can be used to deliver a protein coding sequence over two or more viral vectors (such as AAVs), resulting in reconstitution of the full-length protein in a cell. Such methods can be used to deliver a protein involved in editing a nucleic acid molecule, for example to treat a genetic disease or cancer.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
Exposure of ADRB1-expressing T cells to catecholamines suppresses cytokine production and impairs T cell proliferation. Genetic or pharmacological ablation of β-adrenergic signaling via ADRB1 reduces development of T cell exhaustion in a chronic infection model and improves cytotoxic functions in tumor-infiltrating lymphocytes (TILs) when combined with immune checkpoint blockade (ICB) therapy in a melanoma model. In an ICB-resistant tumor model of murine pancreatic cancer, beta-blockers and ICB synergize to enhance and reprogram T cell responses. Disclosed are modified PBMCs with decreased ADRB1 and/or ADRB2 function, and their use to treat cancer and viral infection. Also disclosed are modified PBMCs with increased ADRB1 and/or ADRB2 function, and their use to treat autoimmune diseases.
Epigenomic and transcriptomic data were used to identify transcription factors (TFs) that define different CD8+TermTerm RMZscan20, TermTermin vivoRMZscan20Jdp2Nfil3Znf324Term Term drivers.
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 15/11 - DNA or RNA fragments; Modified forms thereof
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
15.
MULTIPLEX CRISPR/Cas9-MEDIATED TARGET GENE ACTIVATION SYSTEM
Provided herein are multiplex crRNAs and multiplex sgRNAs, as well as RNA molecules thereof. Also provided are compositions and kits including the multiplex crRNAs and sgRNAs, which can be used in a multiplex targeted gene activation (mTGA) system. Also provided are methods that include administering a therapeutically effective amount of the mTGA system to a subject. In some examples, the method treats a disease associated with reduced or no expression of a gene, such as type I diabetes, Duchenne muscular dystrophy, a liver disease, or acute kidney disease.
Synthetic adenoviruses with liver detargeting mutations and expressing an adenovirus type 34 (Ad34) fiber protein, or a chimeric fiber protein with an Ad34 knob domain, are described. The synthetic adenoviruses traffic to sites of tumors. Use of the synthetic adenoviruses for delivering diagnostic or therapeutic transgenes to tumors are also described.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
Flavone derivatives and pharmaceutical compositions including the derivatives are disclosed. In some instances, the compounds have increased aqueous solubility, bioavailability, and ability to cross the blood-brain-barrier. The compounds may be used to inhibit CK2 activity and/or to treat diseases and conditions mediated at least in part by CK2 enzyme.
A61K 47/55 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting 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 the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug, i.e. a dimer, oligomer or polymer of pharmacologically or therapeutically active compounds
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
A61P 29/00 - Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE (USA)
CALIFORNIA INSTITUTE OF TECHNOLOGY (USA)
THE SALK INSTITUTE FOR BIOLOGICAL STUDIES (USA)
Inventor
Friedman, Rick A
Boussaty, Ely
Hoelz, Andre
Olson, Steven
Shaw, Reuben
Abstract
The present disclosure provides compositions and methods for prevention or treatment of hearing loss. In some examples, a composition for preventing or treating hearing loss comprises at least one compound that activates AMPK in at least one hair cell.
A61K 31/437 - 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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 31/4184 - 1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
Compositions for generating a pancreatic beta-like cell population from a population of undifferentiated cells and methods of use thereof, are provided. The method is an 8 stage process interrupted by a priming step, and it includes; using a chemically defined protocol for the efficient generation of pancreatic progenitors (PPs); improved assembly PPs into 3D clusters; a priming step which uses a chemical/factor cocktail (PP-10C) to maintain 3D-PPs status and enhances their potential to differentiate into β cells ;and a 3-step differentiation protocol using select chemical cocktails that efficiently converts PP-10C-treated 3D-PPs into functional β cells.
Compositions for generating a pancreatic beta-like cell population from a population of undifferentiated cells and methods of use thereof, are provided. The method is an 8 stage process interrupted by a priming step, and it includes; using a chemically defined protocol for the efficient generation of pancreatic progenitors (PPs); improved assembly PPs into 3D clusters; a priming step which uses a chemical/factor cocktail (PP-10C) to maintain 3D-PPs status and enhances their potential to differentiate into β cells ;and a 3-step differentiation protocol using select chemical cocktails that efficiently converts PP-10C-treated 3D-PPs into functional β cells.
The disclosed methods result in a population of functional β cells which expresses pancreatic cell markers selected from the group of c-peptide, the transcription factors NKX6.1, PDX1, PAX6, NEUROD1 and are INS+, and which do not express substantial levels Glucagon (GCG).
Compositions for generating a pancreatic beta-like cell population from a population of undifferentiated cells and methods of use thereof, are provided. The method is an 8 stage process interrupted by a priming step, and it includes; using a chemically defined protocol for the efficient generation of pancreatic progenitors (PPs); improved assembly PPs into 3D clusters; a priming step which uses a chemical/factor cocktail (PP-10C) to maintain 3D-PPs status and enhances their potential to differentiate into β cells ;and a 3-step differentiation protocol using select chemical cocktails that efficiently converts PP-10C-treated 3D-PPs into functional β cells.
The disclosed methods result in a population of functional β cells which expresses pancreatic cell markers selected from the group of c-peptide, the transcription factors NKX6.1, PDX1, PAX6, NEUROD1 and are INS+, and which do not express substantial levels Glucagon (GCG).
The functional β cells can be used to treat conditions such as diabetes.
Flavone, quinolinone, quinazolinone, and aurone derivatives are disclosed. The compounds have a structure according to formula I or formula II, or a pharmaceutically acceptable salt, hydrate, stereoisomer, or tautomer thereof. The compounds may inhibit CK2 enzyme activity. Some compounds selectively reduce or inhibit the CK2A2 enzyme subunit over the CK2A1 enzyme subunit.
A61K 31/352 - 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 condensed with carbocyclic rings, e.g. cannabinols, methantheline
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
C07D 311/30 - 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 not hydrogenated in the hetero ring, e.g. flavones
21.
DNA METHYLATION BARCODES FOR IDENTIFYING BRAIN CELLS
Methods are provided for identifying a brain cell in a biological sample, based on the methylation status of multiple methylation markers in genomic DNA. Also provided are kits that can be used for such methods.
A61P 25/00 - Drugs for disorders of the nervous system
C12Q 1/6837 - Enzymatic or biochemical coupling of nucleic acids to a solid phase using probe arrays or probe chips
C12Q 1/6881 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for tissue or cell typing, e.g. human leukocyte antigen [HLA] probes
G16B 20/00 - ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
22.
MODULATING REGULATORY T CELL FUNCTION IN AUTOIMMUNE DISEASE AND CANCER
Methods of modulating regulatory T (Treg) suppressor activity are provided. Also provided are methods of treating autoimmune diseases and methods of treating cancer. The methods include increasing or reducing the expression or activity of bromodomain-containing 9 (Brd9), bromodomain-containing 7 (Brd7), and/or polybromo 1 (Pbrm1) in a Treg cell or in a subject.
The invention features pancreatic islet and pancreatic organoids, and cell cultures and methods that are useful for the rapid and reliable generation of pancreatic islet and pancreatic islet organoids. The invention also features methods of treating pancreatic diseases and methods of identifying agents that are useful for treatment of pancreatic diseases, such as type 2 diabetes and pancreatic cancer, using the pancreatic islet and pancreatic organoids of the invention.
Provided herein are, inter alia, are media compositions useful for culturing neural cells. In particular, the compositions provided herein mimic important physiological conditions in the living brain and sustain neural activity. The media compositions provided herein improve the efficiency of human neuron maturation and promote synaptic function in long-term in vitro cultures.
CARMEL HAIFA UNIVERSITY ECONOMIC CORPORATION LTD. (Israel)
SALK INSTITUTE FOR BIOLOGICAL STUDIES (USA)
NOVA SCOTIA HEALTH AUTHORITY (Canada)
Inventor
Stern, Shani
Gage, Fred
Alda, Martin
Mizrahi, Liron
Abstract
A system and method of predicting disposition of a mental disorder of a subject may include obtaining a Lymphoblastoid Cell Line (LCL) assay of the subject; calculating a gene expression profile of the subject based on the LCL assay, wherein said gene expression profile comprises a plurality of gene expression levels, each representing quantity of a respective RNA molecule in the LCL assay; providing a first machine-learning (ML) based model, pretrained to predict disposition of a mental disorder based on gene expression profile data; and applying the first ML-based model on the gene expression profile of the subject, to predict disposition of the mental disorder in the subject.
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
C12Q 1/6881 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for tissue or cell typing, e.g. human leukocyte antigen [HLA] probes
G01N 33/68 - Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
G06F 17/18 - Complex mathematical operations for evaluating statistical data
G16B 30/00 - ICT specially adapted for sequence analysis involving nucleotides or amino acids
G16B 40/00 - ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
G16H 20/10 - ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to drugs or medications, e.g. for ensuring correct administration to patients
G16H 50/20 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
27.
METHODS AND COMPOSITIONS FOR MULTIPLEXED SINGLE-CELL 3D SPATIAL GENE EXPRESSION ANALYSIS IN PLANT TISSUE
The present disclosure provides a multiplexed fluorescence in situ hybridization method that enables single-cell and spatial analysis of gene expression in plant tissue in a transgene-free manner. The present disclosure provides methods and compositions of spatially mapping at least one gene in plant tissue in situ. Also provided is a kit for spatially mapping a plurality of genes in plant tissue in situ. In some embodiments, the method comprises hybridizing a plurality of DNA probes with target RNA molecules transcribed from at least one gene. In some embodiments, the method comprises amplifying said probes having barcodes by rolling circle amplification; detecting a plurality of amplified signals from said probes by a sequence-by hybridization, thereby identifying location of the target RNA molecules. In some embodiments, the method comprises obtaining three dimensional gene expression map with the plurality of the genes.
The invention provides compositions featuring TRP-4 polypeptides and polynucleotides, methods for expressing such polypeptides and polynucleotides in a cell type of interest, and methods for inducing the activation of the TRP-4 polypeptide in neurons and other cell types using ultrasound.
Disclosed herein are homology-independent targeted integration methods of integrating an exogenous DNA sequence into a genome of a non-dividing cell and compositions for such methods. Methods herein comprise contacting the non-dividing cell with a composition comprising a targeting construct comprising the exogenous DNA sequence and a targeting sequence, a complementary strand oligonucleotide homologous to the targeting sequence, and a nuclease, thereby altering the genome of the non-dividing cell.
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 diseases; Gene 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
Synthetic adenoviruses with tropism to bone tissue are described. The synthetic adenoviruses include an adenovirus type 11 (Ad11) fiber protein or a chimeric adenovirus fiber protein having an Ad11 knob domain. The synthetic adenoviruses can also include a transgene, such as a reporter gene or a transgene encoding a factor that promotes bone regeneration or repair. Use of the synthetic adenoviruses to target bone tissue and/or to promote bone repair or regeneration is also described.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
A61P 19/08 - Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
Provided and described are bacterial mechanosensory polypeptide and encoding polynucleotide products and compositions thereof, methods of expressing such polypeptides and polynucleotides in a cell type of interest, and methods of inducing and/or modifying the activity or function of various types of cells, including neurons, which express exogenous bacterial mechanosensory polypeptides, using ultrasound.
C07K 14/195 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
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
C12N 13/00 - Treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic waves
33.
SONOGENETIC STIMULATION OF CELLS EXPRESSING A HETEROLOGOUS MECHANOSENSITIVE PROTEIN
Provided and described are mechanosensory polypeptides and encoding polynucleotide products and compositions thereof, methods of expressing such polypeptides and polynucleotides in a cell type of interest, and methods of inducing and/or modifying the activity and/or function of various types of cells that express the exogenous mechanosensory polypeptides using ultrasound.
C12N 13/00 - Treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic waves
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
34.
PATIENT SELECTION BIOMARKERS FOR TREATMENT WITH ULK INHIBITORS
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
A61K 31/505 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
The present disclosure relates to nucleic acid promoter sequences that are able to specifically express genes operatively linked to the promoter in brainstem and spinal motor neuron cells, and to methods for using such promoters to selectively express genes in motor neurons in vitro and in vivo. It is based, at least in part, on the discovery that the nucleic acid of SEQ ID NO: 1 functioned as a motor neuron-specific promoter and was successful in expressing transgenes in motor neuron cells in vivo. The present disclosure also relates to compositions that can increase the activity or expression level of miR-218 and to compositions that can decrease the expression of miR-218 target nucleic acids.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
A61K 31/7088 - Compounds having three or more nucleosides or nucleotides
C12N 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
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 31/713 - Double-stranded nucleic acids or oligonucleotides
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
37.
COMPOSITIONS AND METHODS FOR INCREASING PERIDERM IN PLANT ROOTS
The present disclosure provides methods for increasing periderm, suberin monomers, and overall suberin production in plants. The present disclosure further provides alteration of gene expression associated with periderm and suberin production in plant roots and methods of altering the gene products by gene-editing systems. Also, provided are compositions for generating plants that possess increased amounts of periderm and/or increased amounts of suberin monomers in their roots as compared to control plants as well as the gene-edited plants possessing said traits.
Described herein are compositions featuring TRPA1 polypeptides and polynucleotides, methods for expressing such polypeptides and polynucleotides in a cell type of interest, and methods for inducing the activation of the TRPA1 polypeptide in neurons and other cell types using ultrasound.
A61K 41/00 - Medicinal preparations obtained by treating materials with wave energy or particle radiation
A61K 38/17 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
A61P 25/00 - Drugs for disorders of the nervous system
G16H 50/50 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for simulation or modelling of medical disorders
King Abdullah University of Science and Technology (Saudi Arabia)
Salk Institute for Biological Studies (USA)
Inventor
Magistretti, Pierre Julius
Izpisua Belmonte, Juan Carlos
Hernandez Benitez, Reyna
Abstract
Compositions and methods modulating the steady state of cells are provided. The compositions include metabolites (C1 metabolites and C1 metabolite cocktails (C1-MIM) for use in inducing cells into a different state from their steady state, for example, into a less differentiated state, when compared to their original state before treatment. The C1 metabolites include methionine, SAM (S-adenosyl methionine), threonine, glycine, putrescine, and cysteine. The metabolites are used to supplement cell culture media, and accordingly, cells culture media supplemented with the disclosed metabolites (MIM supplemented media) are also provided.
Compositions and methods modulating the steady state of cells are provided. The compositions include metabolites (C1 metabolites and C1 metabolite cocktails (C1-MIM) for use in inducing cells into a different state from their steady state, for example, into a less differentiated state, when compared to their original state before treatment. The C1 metabolites include methionine, SAM (S-adenosyl methionine), threonine, glycine, putrescine, and cysteine. The metabolites are used to supplement cell culture media, and accordingly, cells culture media supplemented with the disclosed metabolites (MIM supplemented media) are also provided.
The method includes: contacting a cell with the C1 metabolites for a sufficient period of time to result in reprograming the cell into a different state from their steady, for example, into a less differentiated state having progenitor-like characteristics (MIM-Cells). Isolated MIM-cells and their progeny, can be used in a number of applications, including cell therapy and tissue engineering.
Oncolytic adenoviruses capable of selectively replicating in tumor cells deficient in p53 transcriptional activity are described. Recombinant adenovirus genomes that encode the p53-selective adenoviruses are also described. The recombinant adenoviruses and adenovirus genomes, or compositions thereof, can be used, for example, to reduce or inhibit tumor progression, or reduce tumor volume in a subject with a tumor having dysregulated p53 activity.
Recombinant adenovirus genomes that include a synthetic transcriptional circuit are described. Synthetic adenoviruses positively regulated using two-step transcriptional amplification (TSTA) are further described. Selection of the heterologous promoter is based on the desired replication characteristics of the synthetic virus. For example, the heterologous promoter can be a constitutive promoter, a tumor-specific promoter or a tissue-specific promoter.
Methods of lowering blood glucose and treating Type 2 diabetes in a subject by increasing expression or activity of phosphodiesterase 4D isoform 3 (PDE4D3) in adipocytes of the subject are described. In some instances, expression of PDE4D3 in adipocytes is increased by administering a vector that expresses PDE4D3 specifically in adipocytes, or via gene editing by introduction of a PDE4D3-encoding nucleic acid into adipocytes. Use of small molecule activators of PDE4D3 that are targeted to adipocytes is also described.
The disclosure provides nucleic acid constructs that include a TPR-domain suppressor of STIMPY (TSS) promoter operably linked to an isopentenyl-transferase 7 (IPT7) coding sequence. The introduction of such a construct into a plant or plant cell generates transgenic plants having increased root mass and greater carbon sequestration capacity. Plants generated using the methods are provided. Such plants can include other desirable traits.
The present disclosure provides compositions and methods for regulating ethylene signaling in a plant or a plant tissue culture. The present disclosure also provides compositions and methods for modulating gravitropic set-point angle in plant roots via regulation of ethylene signaling. The present disclosure fruther provides small molecules that regulate ethylene signaling.
A61K 31/437 - 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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
A61P 43/00 - Drugs for specific purposes, not provided for in groups
A61K 31/4045 - Indole-alkylamines; Amides thereof, e.g. serotonin, melatonin
G16B 40/00 - ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
G16B 40/00 - ICT specially adapted for biostatistics; ICT specially adapted for bioinformatics-related machine learning or data mining, e.g. knowledge discovery or pattern finding
SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE (USA)
Inventor
Cosford, Nicholas D.P.
Bakas, Nicole A.
Vamos, Mitchell
Shaw, Reuben J.
Limpert, Allison S.
Brun, Sonja N.
Abstract
The present disclosure is directed to compounds, compositions, formulations and methods of use thereof in the treatment and prevention of ULK mediated diseases, including cancer.
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
C07D 401/12 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 401/14 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
50.
MONO AND COMBINATION THERAPIES WITH ULK1/2 INHIBITORS
SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE (USA)
Inventor
Cosford, Nicholas D.P.
Shaw, Reuben J.
Bakas, Nicole A.
Limpert, Allison S.
Brun, Sonja N.
Vamos, Mitchell
Abstract
Provided herein are methods of treating diseases, including cancer, with ULK inhibitors, both as monotherapies and in combination with other therapeutic agents.
Provided herein are blastoids and methods for producing the same that are obtained from an extended pluripotent stem (EPS) cell. The herein-disclosed methods provide a unique and highly malleable in vitro system for studying early preimplantation development. Also provided are EPS-blastoids derived from a somatic cell.
Provided are methods for identification of DNA repair locations in a genome of a non-dividing cell, by incorporating a reactive nucleoside analogs into the genome of the non-dividing cell, then sequencing the regions of the genome that incorporated the nucleoside analog.
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
53.
Methods and Systems for Blazed Mirror Oblique Plane Microscopy (OPM) Imaging of Oblique Planes
Some embodiments of the present disclosure disclose methods and systems for imaging oblique planes of a sample using oblique plane microscopes employing blazed minors. Such a system can include a first optical sub-assembly, a blazed mirror and a second optical sub-assembly, wherein the first optical sub-assembly is configured to receive light beams from an oblique plane of a sample and produce intermediate light beams that are reflected by the blazed mirror to the second optical sub-assembly so that the latter can produce an image of the oblique plane of the sample.
SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE (USA)
Inventor
Cosford, Nicholas D.P.
Bakas, Nicole A.
Shaw, Reuben J.
Limpert, Allison S.
Brun, Sonja N.
Abstract
The present disclosure is directed to compounds, compositions, formulations and methods of use thereof in the treatment and prevention of ULK mediated diseases, including cancer.
The present disclosure provides FGF1 mutant proteins, which selectively bind to/activate FGFR1b. Also provided are nucleic acid molecules that encode such proteins, and vectors and cells that include such nucleic acids. Methods of using the disclosed FGF1 mutants to reduce blood glucose in a mammal and treat a metabolic disorder are provided.
Recombinant adenovirus genomes that include an exogenous open reading frame (ORF) and a self-cleaving peptide coding sequence are described. Optimal placement of the exogenous genes for minimal impact on viral kinetics is further disclosed. Therapeutic applications of the recombinant adenoviruses are also described.
Electro-optical microprobes and methods for forming and using the electro-optical microprobes are disclosed. In one aspect, an electro-optical microprobe includes an optical waveguide including first and second ends and a side surface between the first and the second ends, a first layer including a first electrically conductive material disposed over the side surface of the optical waveguide, a second layer including an electrically conductive polymer disposed on a portion of the first layer proximate to the first end of the optical waveguide, and an isolation layer including an electrically insulative material disposed the second layer and a remaining portion of the first layer that is not covered by the second layer.
The invention features compositions and methods treating or preventing for age-related insulin resistance, type 2 diabetes and related disorders. The method involves depleting fTreg cells with an anti-ST2 antibody to decrease age-related fTreg accumulation and restore insulin sensitivity, thereby treating age-related insulin resistance, type 2 diabetes and related disorders.
C12Q 1/68 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
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 39/395 - Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
A61P 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
Methods are provided for treating osteoarthritis by administering αKlotho protein and sTGFβ-R2 protein to a site within a mammal exhibiting symptoms of osteoarthritis, such as a knee joint. The αKlotho protein and the sTGFβ-R2 protein are both present at the osteoarthritic site.
A61K 38/17 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans
A61P 19/02 - Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
A system of ultrasound based cellular stimulation may include a stimulation apparatus and a stimulation controller. The stimulation apparatus may include a transducer element formed from a single crystal piezoelectric material such as lithium niobate. The stimulation apparatus may deliver high magnitudes of acoustic pressure relative to its dimensions (e.g., size, weight, and/or the like) and without significant heating. The stimulation controller may determine a cellular response to ultrasound stimulation such as membrane deflection and transmembrane voltage change. The stimulation controller may determine, based on the predicted cellular response, parameters for an ultrasound stimulation treatment for a patient such as a magnitude and/or duration of an ultrasonic stimulus for achieving a desired magnitude of membrane deflection and/or transmembrane voltage changes. The ultrasound stimulation treatment may be administered to the patient by the stimulation apparatus operating in accordance with the parameters.
B06B 1/00 - Processes or apparatus for generating mechanical vibrations of infrasonic, sonic or ultrasonic frequency
C12N 13/00 - Treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic waves
H01L 41/04 - SEMICONDUCTOR DEVICES; ELECTRIC SOLID STATE DEVICES NOT OTHERWISE PROVIDED FOR - Details thereof - Details of piezo-electric or electrostrictive elements
62.
METHODS AND COMPOSITIONS FOR EXPRESSION OF EDITING PROTEINS
Provided herein are compositions and systems for reconstitution of RNA molecules, including methods for using these molecules. For example, such molecules can be used to deliver a protein coding sequence over two or more viral vectors (such as AAVs), resulting in reconstitution of the full-length protein in a cell. Such methods can be used to deliver a protein involved in editing a nucleic acid molecule, for example to treat a genetic disease or cancer.
Provided herein are multiplex crRNAs and multiplex sgRNAs, as well as RNA molecules thereof. Also provided are compositions and kits including the multiplex crRNAs and sgRNAs, which can be used in a multiplex targeted gene activation (mTGA) system. Also provided are methods that include administering a therapeutically effective amount of the mTGA system to a subject. In some examples, the method treats a disease associated with reduced or no expression of a gene, such as type I diabetes, Duchenne muscular dystrophy, a liver disease, or acute kidney disease.
Provided herein are multiplex crRNAs and multiplex sgRNAs, as well as RNA molecules thereof. Also provided are compositions and kits including the multiplex crRNAs and sgRNAs, which can be used in a multiplex targeted gene activation (mTGA) system. Also provided are methods that include administering a therapeutically effective amount of the mTGA system to a subject. In some examples, the method treats a disease associated with reduced or no expression of a gene, such as type I diabetes, Duchenne muscular dystrophy, a liver disease, or acute kidney disease.
Provided herein are methods and compositions for editing a target genome in a cell comprising contacting the cell with (i) a single homology arm construct comprising a replacement sequence and a targeted endonuclease cleavage site; and (ii) a targeted endonuclease, wherein the replacement sequence comprises at least one nucleotide difference compared to the target genome and wherein the target genome comprises a sequence homologous to the targeted endonuclease cleavage site.
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 generally features compositions comprising induced pluripotent stem cell progenitors (also termed reprogramming progenitor cells) and methods of isolating such cells. The invention also provides compositions comprising induced pluripotent stem cells (iPSCs) derived from such progenitor cells. Induced pluripotent stem cell progenitors generate iPSCs at high efficiency.
Compositions for generating a pancreatic beta-like cell population from a population of undifferentiated cells and methods of use thereof, are provided. The method is an 8 stage process interrupted by a priming step, and it includes; using a chemically defined protocol for the efficient generation of pancreatic progenitors (PPs); improved assembly PPs into 3D clusters; a priming step which uses a chemical/factor cocktail (PP-10C) to maintain 3D-PPs status and enhances their potential to differentiate into β cells;and a 3-step differentiation protocol using select chemical cocktails that efficiently converts PP-10C-treated 3D-PPs into functional β cells. The disclosed methods result in a population of functional β cells which expresses pancreatic cell markers selected from the group of c-peptide, the transcription factors NKX6.1, PDX1, PAX6, NEUROD1 and are INS+, and which do not express substantial levels Glucagon (GCG). The functional β cells can be used to treat conditions such as diabetes.
SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE (USA)
CALIFORNIA INSTITUTE OF TECHNOLOGY (USA)
THE SALK INSTITUTE FOR BIOLOGICAL STUDIES (USA)
Inventor
Friedman, Rick A.
Boussaty, Ely
Hoelz, Andre
Olson, Steven
Shaw, Reuben
Abstract
The present disclosure provides compositions and methods for prevention or treatment of hearing loss. In some examples, a composition for preventing or treating hearing loss comprises at least one compound that activates AMPK in at least one hair cell.
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/437 - 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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
69.
MODULATING REGULATORY T CELL FUNCTION IN AUTOIMMUNE DISEASE AND CANCER
Methods of modulating regulatory T (Treg) suppressor activity are provided. Also provided are methods of treating autoimmune diseases and methods of treating cancer. The methods include increasing or reducing the expression or activity of bromodomain-containing 9 (Brd9), bromodomain-containing 7 (Brd7), and/or polybromo 1 (Pbrm1) in a Treg cell or in a subject.
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
C12N 5/00 - Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
70.
COMPOSITIONS AND METHODS FOR HIGH-EFFICIENCY RECOMBINATION OF RNA MOLECULES
Provided herein are compositions and systems for reconstitution of RNA molecules, including methods for using these molecules. For example, such molecules can be used to deliver a protein coding sequence over two or more viral vectors (such as AAVs), resulting in reconstitution of the full-length protein in a cell. Such methods can be used to deliver a therapeutic protein, for example to treat a genetic disease or cancer.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
C12N 15/115 - Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith
C12N 15/64 - General methods for preparing the vector, for introducing it into the cell or for selecting the vector-containing host
The invention features pancreatic islet and pancreatic organoids, and cell cultures and methods that are useful for the rapid and reliable generation of pancreatic islet and pancreatic islet organoids. The invention also features methods of treating pancreatic diseases and methods of identifying agents that are useful for treatment of pancreatic diseases, such as type 2 diabetes and pancreatic cancer, using the pancreatic islet and pancreatic organoids of the invention.
Provided and described are mechanosensory polypeptides and encoding polynucleotide products and compositions thereof, methods of expressing such polypeptides and polynucleotides in a cell type of interest, and methods of inducing and/or modifying the activity and/or function of various types of cells that express the exogenous mechanosensory polypeptides using ultrasound.
G01N 29/00 - Investigating or analysing materials by the use of ultrasonic, sonic or infrasonic waves; Visualisation of the interior of objects by transmitting ultrasonic or sonic waves through the object
74.
SONOGENETIC STIMULATION OF CELLS EXPRESSING A HETEROLOGOUS MECHANOSENSITIVE PROTEIN
Provided and described are mechanosensory polypeptides and encoding polynucleotide products and compositions thereof, methods of expressing such polypeptides and polynucleotides in a cell type of interest, and methods of inducing and/or modifying the activity and/or function of various types of cells that express the exogenous mechanosensory polypeptides using ultrasound.
G01N 29/00 - Investigating or analysing materials by the use of ultrasonic, sonic or infrasonic waves; Visualisation of the interior of objects by transmitting ultrasonic or sonic waves through the object
75.
SONOGENIC STIMULATION OF CELLS EXPRESSING BACTERIALLY-DERIVED MECHANOSENSITIVE PROTEINS
Provided and described are bacterial mechanosensory polypeptide and encoding polynucleotide products and compositions thereof, methods of expressing such polypeptides and polynucleotides in a cell type of interest, and methods of inducing and/or modifying the activity or function of various types of cells, including neurons, which express exogenous bacterial mechanosensory polypeptides, using ultrasound.
A61B 8/00 - Diagnosis using ultrasonic, sonic or infrasonic waves
G01N 29/00 - Investigating or analysing materials by the use of ultrasonic, sonic or infrasonic waves; Visualisation of the interior of objects by transmitting ultrasonic or sonic waves through the object
76.
SONOGENIC STIMULATION OF CELLS EXPRESSING BACTERIALLY-DERIVED MECHANOSENSITIVE PROTEINS
Provided and described are bacterial mechanosensory polypeptide and encoding polynucleotide products and compositions thereof, methods of expressing such polypeptides and polynucleotides in a cell type of interest, and methods of inducing and/or modifying the activity or function of various types of cells, including neurons, which express exogenous bacterial mechanosensory polypeptides, using ultrasound.
C12N 13/00 - Treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic waves
G01N 29/00 - Investigating or analysing materials by the use of ultrasonic, sonic or infrasonic waves; Visualisation of the interior of objects by transmitting ultrasonic or sonic waves through the object
Provided herein are synthetic RNA molecules for reconstitution of RNA molecules, including compositions and methods of using these molecules. For example, such molecules can be used to deliver a protein coding sequence over two or more viral vectors (such as AAVs), resulting in reconstitution of the full-length protein in a cell. Such methods can be used to deliver a therapeutic protein, for example to treat a genetic disease or cancer.
Described herein are systems, software, and methods for generating training datasets for machine learning (ML) applications. The systems, software, and methods generally operate by obtaining first and second pluralities of images of a subject bearing as associated imaging label, identifying locations of the imaging label within the first plurality of images, and using the identified locations to generate a plurality of labeled images based upon the second plurality of images. In this manner, a large collection of labeled images may be collected without the need for manual labeling by a human actor. This large collection of labeled images may then form the training set for training a ML system.
C12Q 1/6809 - Methods for determination or identification of nucleic acids involving differential detection
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
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
A61K 31/505 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
A61K 35/00 - Medicinal preparations containing materials or reaction products thereof with undetermined constitution
A61K 45/00 - Medicinal preparations containing active ingredients not provided for in groups
82.
PATIENT SELECTION BIOMARKERS FOR TREATMENT WITH ULK INHIBITORS
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
C12Q 1/6883 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
An adenovirus comprising an E1A polypeptide comprising one or more modifications and comprising an E4orf6/7 polypeptide comprising one or more modifications is described. Compositions and kits comprising the modified adenoviruses are also described. Further described is a method of treating a proliferative disorder in a subject comprising administering to the subject an adenovirus comprising the E1A polypeptide comprising one or more modifications and comprising the E4orf6/7 polypeptide comprising one or more modifications.
Transgenic plants and methods for terpenoid production leveraging such transgenic plants are provided. Such transgenic plants may comprise a first heterologous nucleic acid encoding a polypeptide having 3-hydroxy-3-methylglutarylCoA reductase activity and a second heterologous nucleic acid encoding a polypeptide that introduces de novo formation of isopentenyl phosphate in the plant. Such de novo IP production may be achieved through the overexpression of phosphomevalonate decarboxylase in conjunction with 3-hydroxy-3-methylglutarylCoA reductase, which can result in up to a 130-fold increase of terpenoid production as compared to a wild-type plant.
Recombinant adenovirus genomes that include a heterologous open reading frame (ORF) and a self-cleaving peptide coding sequence are described. The recombinant adenovirus genomes and recombinant adenoviruses produced by the disclosed genomes can be used, for example, in high-throughput assays to measure virus replication kinetics. Methods for measuring replication kinetics of a recombinant adenovirus are also described.
Described herein are compositions featuring TRPA1 polypeptides and polynucleotides, methods for expressing such polypeptides and polynucleotides in a cell type of interest, and methods for inducing the activation of the TRPA1 polypeptide in neurons and other cell types using ultrasound.
Described herein are compositions featuring TRPA1 polypeptides and polynucleotides, methods for expressing such polypeptides and polynucleotides in a cell type of interest, and methods for inducing the activation of the TRPA1 polypeptide in neurons and other cell types using ultrasound.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
A61K 38/17 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans
Recombinant adenovirus genomes that include a synthetic transcriptional circuit are described. Synthetic adenoviruses positively regulated using two-step transcriptional amplification (TSTA) are further described. Selection of the heterologous promoter is based on the desired replication characteristics of the synthetic virus. For example, the heterologous promoter can be a constitutive promoter, a tumor-specific promoter or a tissue-specific promoter.
Oncolytic adenoviruses capable of selectively replicating in tumor cells deficient in p53 transcriptional activity are described. Recombinant adenovirus genomes that encode the p53-selective adenoviruses are also described. The recombinant adenoviruses and adenovirus genomes, or compositions thereof, can be used, for example, to reduce or inhibit tumor progression, or reduce tumor volume in a subject with a tumor having dysregulated p53 activity.
Oncolytic adenoviruses capable of selectively replicating in tumor cells deficient in p53 transcriptional activity are described. Recombinant adenovirus genomes that encode the p53-selective adenoviruses are also described. The recombinant adenoviruses and adenovirus genomes, or compositions thereof, can be used, for example, to reduce or inhibit tumor progression, or reduce tumor volume in a subject with a tumor having dysregulated p53 activity.
Recombinant adenovirus genomes that include a synthetic transcriptional circuit are described. Synthetic adenoviruses positively regulated using two-step transcriptional amplification (TSTA) are further described. Selection of the heterologous promoter is based on the desired replication characteristics of the synthetic virus. For example, the heterologous promoter can be a constitutive promoter, a tumor-specific promoter or a tissue-specific promoter.
Chromen-4-one derivatives, such as e.g. flavone derivatives and pharmaceutical compositions thereof are disclosed. In some instances, the compounds have increased aqueous solubility, bioavailability, and ability to cross the blood-brain-barrier. The compounds may be used to inhibit casein kinase 2 (CK2) activity and/or to treat diseases and conditions mediated at least in part by CK2 enzyme, such as e.g. inflammation, in particular neuroinflammation, or other diseases, such as e.g. cancer, cardiac hypertrophy, cystic fibrosis, a neurodegenerative disease, bipolar disorder, depression, a viral infection, obesity, diabetes mellitus, atherosclerosis, epilepsy, or any combination thereof.
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
A61K 31/352 - 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 condensed with carbocyclic rings, e.g. cannabinols, methantheline
A61K 31/41 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which is nitrogen, e.g. tetrazole
A61K 31/416 - 1,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
A61K 31/4162 - 1,2-Diazoles condensed with heterocyclic ring systems
A61K 31/4184 - 1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
A61K 31/422 - Oxazoles not condensed and containing further heterocyclic rings
A61K 31/423 - Oxazoles condensed with carbocyclic rings
A61K 31/424 - Oxazoles condensed with heterocyclic ring systems, e.g. clavulanic acid
A61K 31/4433 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with oxygen as a ring hetero atom
A61K 31/4439 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
A61K 31/444 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. amrinone
A61K 31/453 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with oxygen as a ring hetero atom
A61K 31/53 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/5383 - 1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
C07D 311/22 - Benzo [b] pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
C07D 401/10 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
C07D 405/04 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 405/06 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07D 405/12 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
C07D 407/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 407/06 - Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07D 413/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 413/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
The invention features cells, islet-like cells, pancreatic islets and organoids (e.g., human islet-like organoids or HILOs), as well as cell cultures and methods that are useful for the rapid and reliable generation of cells and organoids, such as pancreatic islets and organoids, that are sustainable in vivo and that evade immune detection, rejection and autoimmunity. The invention also features methods of treating pancreatic diseases, such as type 2 diabetes, and pancreatic cancer, using the cells, islet-like cells, pancreatic islets and organoids (e.g., HILOs) that are designed to modulate the activity of immune cells that would otherwise react against them.
Chromen-4-one derivatives, such as e.g. flavone derivatives and pharmaceutical compositions thereof are disclosed. In some instances, the compounds have increased aqueous solubility, bioavailability, and ability to cross the blood-brain-barrier. The compounds may be used to inhibit casein kinase 2 (CK2) activity and/or to treat diseases and conditions mediated at least in part by CK2 enzyme, such as e.g. inflammation, in particular neuroinflammation, or other diseases, such as e.g. cancer, cardiac hypertrophy, cystic fibrosis, a neurodegenerative disease, bipolar disorder, depression, a viral infection, obesity, diabetes mellitus, atherosclerosis, epilepsy, or any combination thereof.
C07D 311/22 - Benzo [b] pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
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
C07D 405/04 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 413/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 405/12 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 413/12 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
C07D 407/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07D 407/06 - Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
C07D 401/10 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
C07D 417/14 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group containing three or more hetero rings
C07D 405/14 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
A61K 31/352 - 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 condensed with carbocyclic rings, e.g. cannabinols, methantheline
A61K 31/443 - Non-condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
96.
TSS PROMOTER INCREASES ROOT MASS AND CARBON SEQUESTRATION
The disclosure provides nucleic acid constructs that include a TPR-domain suppressor of STIMPY (TSS) promoter operably linked to an isopentenyl-transferase 7 (IPT7) coding sequence. The introduction of such a construct into a plant or plant cell generates transgenic plants having increased root mass and greater carbon sequestration capacity. Plants generated using the methods are provided. Such plants can include other desirable traits.
C12N 5/00 - Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
C12N 15/82 - Vectors or expression systems specially adapted for eukaryotic hosts for plant cells
C12N 15/00 - Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
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
97.
EXPRESSION OF IPT7 FROM TSS PROMOTER INCREASES ROOT MASS AND CARBON SEQUESTRATION
The disclosure provides nucleic acid constructs that include a TPR-domain suppressor of STIMPY (TSS) promoter operably linked to an isopentenyl-transferase 7 (IPT7) coding sequence. The introduction of such a construct into a plant or plant cell generates transgenic plants having increased root mass and greater carbon sequestration capacity. Plants generated using the methods are provided. Such plants can include other desirable traits.
A01H 5/00 - Angiosperms, i.e. flowering plants, characterised by their plant parts; Angiosperms characterised otherwise than by their botanic taxonomy
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
C12N 5/00 - Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
C12N 15/00 - Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
C12N 15/82 - Vectors or expression systems specially adapted for eukaryotic hosts for plant cells
