Absolute blood volume in dialysis patients is a useful patient attribute to know for dialysis treatment, diagnosis, adjustments, etc. In some cases, it is difficult or impossible to directly determine absolute blood volume. Estimating absolute blood volume may be used to overcome the inability to directly determine the absolute blood volume. Estimating absolute blood volume may include obtaining a series of measurements of hemoconcentration of a patient over a time period, and estimating parameters for a physiological model based on the series of measurements. The absolute blood volume of the patient may be determined using the physiological model.
A61B 5/00 - Measuring for diagnostic purposes ; Identification of persons
A61B 5/02 - Measuring pulse, heart rate, blood pressure or blood flow; Combined pulse/heart-rate/blood pressure determination; Evaluating a cardiovascular condition not otherwise provided for, e.g. using combinations of techniques provided for in this group with electrocardiography; Heart catheters for measuring blood pressure
A61B 5/0275 - Measuring blood flow using tracers, e.g. dye dilution
A61B 5/145 - Measuring characteristics of blood in vivo, e.g. gas concentration, pH-value
A61M 1/26 - Dialysis systems; Artificial kidneys; Blood oxygenators with membranes which are moving
A61M 1/36 - Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation
2.
SYSTEM AND METHOD FOR ROBOTIC SURGICAL INTERVENTION IN A MAGNETIC RESONANCE IMAGER
A system and method for image guided assisted medical procedures using modular units, such that a controller, under the direction of a computer and imaging device, can be utilized to drive and track low cost, purpose specific manipulators. The system utilizes modular actuators, self tracking, and linkages. The systems can be optimized at a low cost for most effectively performing surgical procedures, while reusing the more costly components of the system, e.g. the control, driving, and tracking systems. The system and method may utilize MRI real time guidance during the above procedures.
Examples described herein provide a computer-implemented method for training a neural network using forward signal propagation learning. The method includes receiving, at a first layer of the neural network, an input value and a label associated with the input value. The method further includes calculating, for the first layer of the neural network, a first loss value based at least in part on outputs of the first layer for the input value and for the label. The method further includes updating, based at least in part on the first loss value, the first layer of the neural network based at least in part on the outputs of the first layer for the input value and for the label.
This disclosure relates to compounds ("siRNASO") comprising a double stranded RNA (dsRNA) attached to antisense oligonucleotides (ASO) and heteroduplex oligonucleotides (HDO). Also provided are methods of inhibiting gene expression with the same.
C12Q 1/70 - Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving virus or bacteriophage
A61K 41/00 - Medicinal preparations obtained by treating materials with wave energy or particle radiation
This disclosure relates to novel C9ORF72 targeting sequences. Novel oligonucleotides for the treatment of neurodegenerative diseases are also provided.
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
A61K 9/00 - Medicinal preparations characterised by special physical form
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
7.
NANOPORE TWEEZER APPROACH FOR PROTEIN KINASE ALLOSTERIC DRUG SCREENING
Disclosed herein are nanopore tweezer systems that can be used to screen for allosteric inhibitors of protein kinases. In some embodiments, the protein kinase is a mutant kinase that confers resistance to chemotherapeutic drugs during cancer treatment. Therefore, the disclosed systems and methods can be used to identify drugs for treating drug resistant cancers.
Novel oligonucleotides that enhance silencing of the expression of a gene containing a single nucleotide polymorphism (SNP) relative to the expression of the corresponding wild-type gene are provided. Methods of using novel oligonucleotides that enhance silencing of the expression of a gene containing a SNP relative to the expression of the corresponding wild-type gene are provided.
A method of forming a flexible electronic component includes treating a flexible fluoroelastomer substrate to increase the surface energy of the substrate to a specified surface energy. After the treatment, a layer of conductive material is printed with an inkjet printer onto the substrate. After the printing, an encapsulant layer comprising a fluoroelastomer is applied onto the substrate.
H05K 3/12 - Apparatus or processes for manufacturing printed circuits in which conductive material is applied to the insulating support in such a manner as to form the desired conductive pattern using printing techniques to apply the conductive material
10.
COMPOSITIONS AND METHODS FOR IMPROVED GENE EDITING
The disclosure provides novel methods and compositions for gene editing. In particular, the disclosure relates to compositions and methods of making modified nucleic acid donor templates for highly efficient and precise gene editing.
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
C12N 15/66 - General methods for inserting a gene into a vector to form a recombinant vector using cleavage and ligation; Use of non-functional linkers or adaptors, e.g. linkers containing the sequence for a restriction endonuclease
C12N 15/90 - Stable introduction of foreign DNA into chromosome
Aspects of the disclosure relate to compositions and methods for epigenetic regulation of endogenous gene expression from viral vectors. In some embodiments, the disclosure provides expression constructs comprising a viral vector encoding a transgene, the activation of which is regulated by a rapamycin/rapalog-based system, and the transgene is capable of epigenetically regulate an endogenous gene.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
A61K 31/7036 - Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin having at least one amino group directly attached to the carbocyclic ring, e.g. streptomycin, gentamycin, amikacin, validamycin, fortimicins
A device may (i) at least one electrode associated with an electric generator to generate a pulsed electric field (PEF) in solid tissue, wherein said electrode comprises more than one hole/opening at the end in contact with said solid tissue and an insulating sleeve that can be adjusted to alter the side hole profile. A device may (ii) a cellular-component extraction element by suction through at least one electrode, wherein upon introducing said at least one electrode into said solid tissue, and generating the PEF, the PEF induces a biophysical response from cells in solid tissue or other condition (such as be blood, in vitro etc.) resulting in at least one cellular component to exit to extracellular matrix which is then extracted by said extraction element.
The present invention relates to the construction of and immunization with viral vaccines. In particular, bivalent vaccines that are capable of providing simultaneous virus infection protection for two or more different viruses. Furthermore, the bivalent vaccines contemplated herein are contemplated as being effective in a neonatal mammal. One such bivalent viral vaccine comprises two antigenic epitopes against the dengue viruses and at least one antigenic epitope against hepatitis B virus. Immunization cross-reactivity may also provide infection protection against other viruses as well.
C12N 15/85 - Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
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
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 31/712 - Nucleic acids or oligonucleotides having modified sugars, i.e. other than ribose or 2'-deoxyribose
A61K 31/7125 - Nucleic acids or oligonucleotides having modified internucleoside linkage, i.e. other than 3'-5' phosphodiesters
A61K 31/713 - Double-stranded nucleic acids or oligonucleotides
A61K 47/54 - 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
Methods of treating or reducing the risk of obesity and/or obesite-related disorders, e.g., metabolic syndrome, hepatic and non-hepatic steatosis, and diabetes, using C20orf27 proteins or nucleic acids.
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
A system for evaluating a cell sample may comprise a specimen slide scanner, a computer-based image analyzer, and an evaluation subsystem. The specimen slide scanner may be configured to acquire images of an entire surface of a microscope slide upon which the cell sample is mounted. The computer-based image analyzer may be configured to identify one or more follicular clusters within each of the images acquired by the specimen slide scanner. The evaluation subsystem may be configured to (i) compare a number of follicular clusters identified by the computer-based image analyzer to an adequacy threshold, and (ii) present an adequacy notification to a user when the number of the follicular clusters identified by the computer-based image analyzer exceeds the adequacy threshold.
A flexible circuit module is disclosed. The flexible circuit module includes a fabric member including a plurality of fibers having non-conductive elements, and conductive elements oriented through the plane of the fabric. Each conductive element includes a first fiber element strand and a first unterminated end opposite the first fiber element strand, and a second fiber element strand having second unterminated end opposite the second fiber element strand. The fabric member further includes a first side with the first fiber element strands extending therefrom and a second side with second fiber element strands extending therefrom. A first hook-and-loop busbar is conductively connected to the first fiber element strands and a second hook-and-loop busbar is conductively connected to the second fiber element strands.
H05K 1/18 - Printed circuits structurally associated with non-printed electric components
H05K 3/32 - Assembling printed circuits with electric components, e.g. with resistor electrically connecting electric components or wires to printed circuits
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 31/7088 - Compounds having three or more nucleosides or nucleotides
A61K 47/54 - 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
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 1/00 - Drugs for disorders of the alimentary tract or the digestive system
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
A61P 5/00 - Drugs for disorders of the endocrine system
A61P 9/00 - Drugs for disorders of the cardiovascular system
A61P 11/00 - Drugs for disorders of the respiratory system
A61P 13/12 - Drugs for disorders of the urinary system of the kidneys
C07H 21/00 - Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
C07H 21/02 - 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 ribosyl as saccharide radical
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 15/11 - DNA or RNA fragments; Modified forms thereof
The present disclosure provides, in some aspects, humanized immunodeficient mouse models that support long-term engraftment and function of human T cells, natural killer cells, and myeloid cells, without the need for conditioning.
The invention provides methods for using virus-like particle (VLP) vaccines containing a stabilized pre-fusion respiratory syncytial virus (RSV) F protein to stimulate RSV neutralizing antibodies in pre-immune subjects. In one embodiment, the invention provides a method for immunizing a mammalian subject in need of immunizing against Respiratory Syncytial virus (RSV) infection, comprising, a) providing i) a pre-immune mammalian subject containing RSV neutralizing antibodies, ii) a first composition comprising recombinant chimeric Newcastle disease virus-like particles (ND VLPs), that contain a chimeric protein comprising, in operable combination, 1) stabilized pre-fusion RSV F protein ectodomain, 2) transmembrane (TM) domain of NDV F protein, and 3) cytoplasmic (CT) domain of NDV F protein, and b) administering an immunologically effective amount of the first composition to the pre-immune subject to produce an immunized subject that comprises an increase in the level of the RSV neutralizing antibodies compared to the level of RSV neutralizing antibodies in the pre-immune subject. In one embodiment, the level of the RSV neutralizing antibodies in the pre-immune subject does not prevent RSV infection of the pre-immune subject.
Aspects of the disclosure relate to compositions and methods useful for treating Huntington's disease. In some embodiments, the disclosure provides interfering nucleic acids (e.g., artificial miRNAs) targeting the huntingtin gene (111 1) and methods of treating Huntington's disease using the same.
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense 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
C12N 7/00 - Viruses, e.g. bacteriophages; Compositions thereof; Preparation or purification thereof
Aspects of the disclosure relate to compositions and methods useful for treating ocular ciliopathies, for example Leber congenital amaurosis (LCA). In some embodiments, the disclosure provides isolated nucleic acids comprising a transgene encoding a CEP290 protein fragment, and methods of treating ocular ciliopathies using the same.
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
C12N 7/00 - Viruses, e.g. bacteriophages; Compositions thereof; Preparation or purification thereof
This disclosure relates to novel targets for angiogenic disorders. Novel oligonucleotides are also provided. Methods of using the novel oligonucleotides for the treatment of angiogenic disorders (e.g., preeclampsia) are also provided.
The present disclosure provides a yeast particle delivery system for controlled release of cannabinoids and other hydrophobic payloads. The disclosure further provides methods of making and methods of using the yeast particle delivery system.
The present disclosure provides an improved yeast particle encapsulated nano-silica delivery system. The disclosure further provides methods of making and methods of using a nano-silica yeast particle delivery system.
A61K 47/69 - 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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
This disclosure relates to methods of treating and diagnosing protein misfolding disorders. In some embodiments, the treatment is with gene therapy, gene editing, or administration of protective proteins.
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
A61K 38/16 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
This disclosure relates to novel PMS1 targeting sequences. Novel PMS1 targeting oligonucleotides for the treatment of trinucleotide repeat disease or disorder are also provided.
C90rf7242C90rf72C90rf72 expression. In some embodiments, described herein are methods of treating amyotrophic lateral sclerosis (ALS) and/or frontotemporal dementia (FTD).
A dispersion includes a plurality of polymer particles, a plurality of inorganic particles, or a combination thereof dispersed in an aqueous solution, wherein the polymer particles, the inorganic particles, or the combination thereof are substantially insoluble in the aqueous solution. At least a portion of the surface of each particle includes one or more functional surfactants disposed on the surface of the particle. The functional surfactants include a C18-32 alkyl group; and at least one functional group that is a sulfonate group, a phosphate group, a ureido group, an acetoacetoxy group, a carboxylate group, a C1-12 fluorocarbon group, a zwitterionic group, a polyether group, a sugar group, a quaternary ammonium group, or a combination thereof. The dispersions can be useful in the preparation of coatings.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
37.
ANTI-ETEC ADHESIN PROTEIN ANTIBODIES AND METHODS OF USE
A method comprises placing in a vessel a mixture having a specified suspended solids or sludge concentration and comprising a water-based reaction medium and at least one microalgae including filamentous cyanobacteria, said water-based reaction medium comprising a nutrient material that is consumable by a live bacterium or by a live protozoan present in said water-based reaction medium, and incubating said mixture for a specified incubation period under at least intermittent illumination with a specified luminous flux during periods of illumination while mixing said mixture under a specified shear stress, wherein said filamentous cyanobacteria forms a supporting matrix that incorporates said live bacterium or said live protozoan into a biologically-active bioaggregate granule, wherein said incubating produces a plurality of said biologically-active bioaggregate granules.
A system includes a sensor, a plurality of cells, and a processor. The sensor includes a plurality of transducers arranged on a planar surface and includes a first transducer and a second transducer. The first transducer is configured to produce an analog output signal corresponding to a detected input signal. The cells are arranged in a network and include a first and a second cell and are disposed proximate the sensor in a three-dimensional stacking fashion. The first transducer and the second transducer are electrically coupled to the first cell and the second cell in one-to-one relation. The first cell includes a plurality of inputs and a first cell output. Each input is coupled to an output of a corresponding plurality of neighboring cells. The first cell includes a first memristor and a bridge circuit configured to receive the analog output signal and provide a current corresponding to the detected input signal in a pixel-parallel fashion. The processor is coupled to the network and generates a parameter associated with a weight for each cell of the plurality of cells.
C07C 13/66 - Polycyclic hydrocarbons or acyclic hydrocarbon derivatives thereof with condensed rings with more than three condensed rings the condensed ring system contains only four rings
Disclosed herein is a composition that involves a nanopore disposed in a membrane preparation, wherein the nanopore has an outer membrane protein G (OmpG) having 8 to 22 β-strands connected by a plurality of flexible loops on a first side of the membrane preparation and a plurality short turns on a second side of the membrane preparation, wherein a heterologous peptide is inserted within one or more of the flexible loops. Also disclosed herein is a method of detecting binding of a ligand to a target, the method involving: exposing a nanopore composition disclosed herein to a target; assessing a gating pattern of the nanopore; and detecting binding of the target to the heterologous peptide based on the gating pattern.
In some aspects, the disclosure relates to methods for improving titer and yield of viral vector production. In some embodiments, the methods comprise transient silencing of transgene expression during packaging of a viral vector.
The present disclosure provides an improved yeast particle encapsulated nano-silica delivery system. The disclosure further provides methods of making and methods of using a nano-silica yeast particle delivery system.
This disclosure relates to novel PMS2 targeting sequences. Novel PMS2 targeting oligonucleotides for the treatment of a trinucleotide repeat disease or disorder are also provided.
This invention is related to the field of genetic engineering. In particular, it is related to compositions and methods to treat genetically-based diseases and disorder or diseases that are caused by the translation of non-functional proteins from an mRNA with a nonsense (premature) stop codon. Nonesense stop codon readthrough results in a full-length protein and restores protein function. For example, a combination of a suppressor transfer ribonucleic acid (stRNA) and nucleic acid antisense oligomers are contemplated that promote translation readthrough of mRNAs with nonsense stop codons.
The present disclosure provides a yeast particle delivery system for controlled release of cannabinoids and other hydrophobic payloads. The disclosure further provides methods of making and methods of using the yeast particle delivery system.
A61K 47/69 - 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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
Droplet-interface bilayer and lipid bilayer membrane compositions stabilized with an amphiphilic polymer are disclosed. Methods of making and using the compositions are also disclosed.
Aspects of the disclosure relate to compositions and methods for modulating bone growth, for example by increasing osteogenesis and/or decreasing osteoclastogenesis. The disclosure is based, in part, on recombinant adeno-associated virus (rAAV) vectors encoding microRNAs or miRNA inhibitors that inhibit endogenous miR-214-3p and/or mediate overexpression of miR-34a-5p in osteoblasts and osteoclasts. In some embodiments, compositions described by the disclosure are useful for treating certain bone diseases or disorders, such as osteoporosis.
Human skeletal muscle stem cells were generated from facioscapulohumeral muscular dystrophy (FSHD) and healthy control iPSC using a transgene-free skeletal muscle differentiation protocol and production of stable iMyoblasts. Analyses revealed that FSHD and healthy control iMyoblasts are embryonic-like myogenic cells that undergo myotube differentiation ex vivo by growth factor depletion and are efficiently transplantable into the tibialis anterior (TA) muscles of NSG mice, where human muscle under-goes embryonic-to-adult myosin isoform switching. The DUX4 FSHD disease gene maintains its hypomethylated disease state inFSHD iPSC and iMyoblast, and its expression is upregulated during myotube differentiation and in muscle xenografts. Consequently, these iMyoblasts accurately exhibit the molecular pathology of human muscular dystrophies and are useful for the development of drug, gene editing and stem cell therapeutics.
Disclosed herein is a composition comprising a cationically polymerizable first epoxide and a second epoxide. The first epoxide is a glycidyl epoxide and the second epoxide further comprises a glycidyl epoxide and/or a non-glycidyl epoxide. The disclosed composition further comprises an initiator and a filler, where the composition upon external stimulus undergoes an ionic polymerization reaction in a spatially propagating reaction front or in a global reaction that occurs throughout an entire composition.
C08G 59/16 - Polycondensates modified by chemical after-treatment by monocarboxylic acids or by anhydrides, halides or low-molecular-weight esters thereof
C09J 163/00 - Adhesives based on epoxy resins; Adhesives based on derivatives of epoxy resins
C08G 59/68 - Macromolecules obtained by polymerising compounds containing more than one epoxy group per molecule using curing agents or catalysts which react with the epoxy groups characterised by the catalysts used
51.
METHODS AND COMPOSITIONS FOR RESTORING STMN2 LEVELS
The disclosure relates to compositions and methods for treating a disease or condition associated with a TDP-pathology or a decline in TDP-43 functionality in neuronal cells in a subject, and for identifying candidate agents to suppress or prevent inclusion of an abortive or altered STMN2 RNA sequence.
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense 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
52.
DEVELOPMENT OF NOVEL GENE THERAPEUTICS FOR INFLAMMATION-INDUCED BONE LOSS
Aspects of the disclosure relate to compositions and methods for reding inflammation and/or inhibiting bone loss (e.g., bone loss induced by inflammation). In some embodiments, the disclosure provides isolated nucleic acids and expression constructs (e.g., rAAVs, etc.) that encode one or more of the following transgenes: inhibitory nucleic acids targeting Schnurri 3 (SHN3), inhibitory nucleic acids targeting Cathepsin K (CTSK), inhibitory nucleic acids targeting sclerostin (SOST), inhibitory nucleic acids targeting receptor activator of NF-κβ (RANK), inhibitory nucleic acids targeting receptor activator of NF-κβ ligand (RANKL), soluble TNF-α Receptor 2 (sTNFR2), and soluble IL-1 Receptor Antagonist (sIL1Rα). In some embodiments, compositions described by the disclosure are useful for treating diseases associated with inflammation, for example rheumatoid arthritis (RA).
A composition for making a filler including a plurality of ceramic particles, an oxirane monomer in liquid form, an ultraviolet initiator that absorbs ultraviolet, and a thermal initiator.
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
A61K 9/00 - Medicinal preparations characterised by special physical form
A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
C12N 15/11 - DNA or RNA fragments; Modified forms thereof
55.
NANODEVICES AND METHODS FOR MEASURING BIOFLUIDIC FLOW USING A GRAPHENE-BASED MICROELECTRODE
The invention provides devices and methods for measuring microfluidic flow velocity. The novel electrical nanodevice employs a single microelectrode of monolayer graphene and measures in real time at high resolution and stability microfluidic flow velocity by quantifying contact electrification-induced current variations.
An alignment key includes: a first multi-focal meta-lens that includes a plurality of first nanostructures, the plurality of first nanostructures having a first shape distribution that forms two different focal lengths with respect to a first set of regions in the first multi-focal meta-lens; and a second multi-focal meta-lens that includes a plurality of second nanostructures, the plurality of second nanostructures having a second shape distribution that forms the two different focal lengths with respect to a second set of regions in the second multi-focal meta-lens.
Extended Nucleic Acid (exNA)-modified crRNAs and tracrRNAs are provided. Methods of using the crRNAs and tracrRNAs for genome editing with a CRISPR nuclease and kits for performing the same are also provided.
A composition for making a filler including a plurality of ceramic particles, an oxirane monomer in liquid form, an ultraviolet initiator that absorbs ultraviolet, and a thermal initiator.
C08G 59/68 - Macromolecules obtained by polymerising compounds containing more than one epoxy group per molecule using curing agents or catalysts which react with the epoxy groups characterised by the catalysts used
In some aspects, the disclosure relates to compositions and methods of engineering a transgene. In some embodiments, the disclosure provides self-regulating recombinant nucleic acids, viral vectors and pharmaceutical compositions comprising a MeCP2 transgene. In some embodiments, compositions and methods described by the disclosure are useful for treating diseases and disorders associated with a loss of function mutation, for example Rett syndrome.
C07K 14/47 - Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from humans from vertebrates from mammals
In some aspects, the disclosure relates to compositions and methods useful for inhibiting SOD1 expression in cells (e.g., cells of a subject). In some embodiments, the disclosure describes isolated nucleic acids engineered to express an inhibitory nucleic acid targeting endogenous SOD1 and an mRNA encoding a hardened SOD1 protein. In some embodiments, compositions and methods described by the disclosure are useful for treating Amyotrophic Lateral Sclerosis (ALS) in a subject.
Composition and methods of diagnosing, monitoring, and treating subjects with a motor neuron pathology, such as motor neuron disorders (including but not limited to amyotrophic lateral sclerosis (ALS)) and neuropathies.
This disclosure relates to novel ATN1 targeting sequences. Novel ATN1 targeting oligonucleotides for the treatment of neurodegenerative diseases are also provided.
The present disclosure provides hyperloaded yeast particles. The disclosure further provides methods of making hyperloaded yeast particles and methods of using hyperloaded yeast particles.
A01N 43/80 - Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms, as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,2
A61K 47/46 - Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
A61K 31/085 - Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
A01N 43/22 - 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 rings with more than six members
Protecting oligonucleotides are provided. Protecting oligonucleotides with 5′ and/or 3′ conjugated moieties are provided. Protecting oligonucleotides with chemical modifications are provided. Methods of using the protecting oligonucleotides for genome editing with a CRISPR nuclease and kits for performing the same are also provided.
The invention provides polymers and polymer-based nano-structures, in particular, polymers and polymer network to which biomolecules (e.g., proteins, antibodies, peptide aptamers) can be covalently conjugated and stably encapsulated therein and be controllably delivered and released upon degradation of the nano-structures in response to specific microenvironment, and compositions and methods of preparation and use thereof.
A61K 47/68 - 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 antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
66.
SYSTEM AND METHOD FOR AUTO-FLOCCULATION OF WASTEWATER
A method comprises the steps of receiving a wastewater containing solid particles in suspension, agitating the wastewater for a specified agitation period under specified agitation conditions sufficient to enable auto-flocculation of at least a portion of the solid particles into flocs to provide an agitated wastewater, allowing the agitated wastewater to settle for a specified sedimentation period to allow at least a portion of the flocs to settle, and separating at least a portion of the settled flocs from the agitated wastewater to provide a clarified wastewater effluent.
B01F 27/90 - Mixers with rotary stirring devices in fixed receptacles; Kneaders with stirrers rotating about a substantially vertical axis with paddles or arms
C02F 1/30 - Treatment of water, waste water, or sewage by irradiation
The instant disclosure provides RNA-modulating agents that function to recruit one or more small regulatory RNA molecules (e.g., miRNA molecules, Y RNAs, and siRNAs) to a target mRNA thereby modulating (e.g., inhibiting) the translation of the target mRNA or destabilizing the mRNA. Methods for using the RNA-modulating agents are also provided.
In one aspect, the invention relates to a method of loading exosomes with oligonucleotide cargo, by incubating an oligonucleotide comprising one or more hydrophobic modifications with a population of exosomes for a period of time sufficient to allow loading of the exosomes with the oligonucleotide. Exosomes loaded with hydrophobically modified oligonucleotide cargo, and uses thereof, are also provided.
C12N 15/88 - Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation using microencapsulation, e.g. using liposome vesicle
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
70.
NOVEL MAIN PROTEASE INHIBITORS, AND COMPOSITIONS AND METHODS THEREOF
The invention provides novel compounds that are potent inhibitors of main protease (MPro) and pharmaceutical compositions and methods thereof for treating MPro-associated or mediated diseases and conditions, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV2).
The present invention relates to the field of genomic engineering. In particular, a chimeric prime editing (cPE) system is disclosed comprising elements including, but not limited to a Cas9 nickase (nCas9)/high fidelity nucleotide polymerase (HFNTPol) RNA, one or more single guide RNAs (sgRNAs), and a chimeric prime editor template oligonucleotide (cpetODN) comprising a deoxyribonucleic acid nucleotide polymerase template (NPT) and a primer binding site. For example, the sgRNA and the cpetODN are ligated into a single oligonucleotide. Alternatively, the sgRNA and the cpetODN are free and independent molecules (e.g., modular). This cPE system results in precise and efficient genome editing in cells and in adult mouse liver which is advantageous over conventional sgRNA prime editor fusion constructs. This flexible and modular system is an improvement in the art to obtain precise genome editing.
A method of autonomous driving by an autonomous vehicle (AV),comprising: detecting (11110), based on sensor data, an environment state; selecting (11120) an action based on the environment state; identifying (11130) a current set of indiscriminate states; identifying (11140) a discriminator from the current set of indiscriminate states; training (11150) a feedback model for the discriminator; determining (11160) an autonomy level associated with the environment state and the action, wherein the autonomy level is selected based at least on an autonomy model and the feedback model; and performing (11170) the action according to the autonomy level.
G05B 13/04 - Adaptive control systems, i.e. systems automatically adjusting themselves to have a performance which is optimum according to some preassigned criterion electric involving the use of models or simulators
This disclosure relates to novel APP targeting sequences. Novel APP targeting oligonucleotides for the treatment of neurodegenerative diseases are also provided.
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense 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
A method comprises flowing a mixture comprising a water-based reaction medium and at least one microalgae into a reaction vessel, wherein the reaction medium comprises a nutrient material that is consumable by a live microalgae, bacterium, or protozoa present in the reaction medium, incubating the mixture under at least intermittent illumination with a specified luminous flux such that the microalgae forms a supporting matrix that incorporates the live microalgae, bacterium, or protozoa into biologically-active bioaggregate granules, selecting out a first specified portion of the biologically-active bioaggregate granules that are smaller than a first specified size or below a first specified weight or selecting out a second specified portion of the biologically-active bioaggregate granules that are larger than a second specified size or over a second specified weight and removing the first and/or the second specified portions of the biologically-active bioaggregate granules in an effluent stream.
A plush toy system comprises a plush toy body with an outer fabric layer, wherein the outer fabric layer forms an interactive surface engageable by a user, an array of textile-based pressure sensors coupled to the plush toy body proximate to the outer fabric layer, and sensor conditioning circuits coupled to the plush toy, the sensor conditioning circuits being configured to interpret signals from the textile-based pressure sensors to identify interaction between the user and the interactive surface.
A first method includes detecting, based on sensor data, an environment state; selecting an action based on the environment state; determining an autonomy level associated with the environment state and the action; and performing the action according to the autonomy level. The autonomy level can be selected based at least on an autonomy model and a feedback model. A second method includes calculating, by solving an extended Stochastic Shortest Path (SSP) problem, a policy for solving a task. The policy can map environment states and autonomy levels to actions and autonomy levels. Calculating the policy can include generating plans that operate across multiple levels of autonomy.
B60W 60/00 - Drive control systems specially adapted for autonomous road vehicles
B60W 50/00 - CONJOINT CONTROL OF VEHICLE SUB-UNITS OF DIFFERENT TYPE OR DIFFERENT FUNCTION; CONTROL SYSTEMS SPECIALLY ADAPTED FOR HYBRID VEHICLES; ROAD VEHICLE DRIVE CONTROL SYSTEMS FOR PURPOSES NOT RELATED TO THE CONTROL OF A PARTICULAR SUB-UNIT - Details of control systems for road vehicle drive control not related to the control of a particular sub-unit
G06N 7/00 - Computing arrangements based on specific mathematical models
A method comprises flowing a mixture comprising a water-based reaction medium and at least one microalgae into a reaction vessel, wherein the reaction medium comprises a nutrient material that is consumable by a live microalgae, bacterium, or protozoa present in the reaction medium, incubating the mixture under at least intermittent illumination with a specified luminous flux such that the microalgae forms a supporting matrix that incorporates the live microalgae, bacterium, or protozoa into biologically-active bioaggregate granules, selecting out a first specified portion of the biologically-active bioaggregate granules that are smaller than a first specified size or below a first specified weight or selecting out a second specified portion of the biologically-active bioaggregate granules that are larger than a second specified size or over a second specified weight and removing the first and/or the second specified portions of the biologically-active bioaggregate granules in an effluent stream.
The invention provides novel polymer-protein conjugates and molecular assemblies for controlled intracellular delivery of proteins, and compositions and methods of preparation and use thereof.
C08F 220/28 - Esters containing oxygen in addition to the carboxy oxygen containing no aromatic rings in the alcohol moiety
A61K 47/65 - Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
A61K 47/60 - 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 macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
A wind turbine system comprises a vessel; a wind turbine mounted to the vessel, the wind turbine comprising rotor blades configured to convert an airstream to rotational shaft power, and an electrical generator configured to convert the rotational shaft power to electrical power; a hydrogen production system configured to be powered by the electrical generator; a propulsion system configured to propel the vessel via power from the electrical generator; and a steering system to control orientation of the vessel relative to the water and the airstream. A method of producing hydrogen comprises floating a vessel in open sea in areas of wind; rotating a wind turbine with the wind to produce electrical energy; synthesizing hydrogen gas from seawater utilizing the electrical energy from the wind turbine; storing the hydrogen gas in a storage system transported by the vessel; and offloading the hydrogen from the storage system.
B63B 1/12 - Hydrodynamic or hydrostatic features of hulls or of hydrofoils deriving lift mainly from water displacement with multiple hulls the hulls being interconnected rigidly
F03D 13/25 - Arrangements for mounting or supporting wind motors; Masts or towers for wind motors specially adapted for offshore installation
F03D 9/32 - Wind motors specially adapted for installation in particular locations on moving objects, e.g. vehicles
B63B 25/12 - Load-accommodating arrangements, e.g. stowing or trimming; Vessels characterised thereby for bulk goods fluid closed
B63H 21/17 - Use of propulsion power plant or units on vessels the vessels being motor-driven by electric motor
B63H 21/21 - Control means for engine or transmission, specially adapted for use on marine vessels
B63B 39/03 - Equipment to decrease pitch, roll, or like unwanted vessel movements; Apparatus for indicating vessel attitude to decrease vessel movements by displacement of masses by transferring liquids
H02K 7/18 - Structural association of electric generators with mechanical driving motors, e.g.with turbines
H02K 11/00 - Structural association of dynamo-electric machines with electric components or with devices for shielding, monitoring or protection
80.
HYPERLOADED YEAST CELL WALL PARTICLE AND USES THEREOF
The present disclosure provides hyperloaded yeast particles. The disclosure further provides methods of making hyperloaded yeast particles and methods of using hyperloaded yeast particles.
A61K 35/66 - Microorganisms or materials therefrom
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61K 47/61 - 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 macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule the organic macromolecular compound being a polysaccharide or a derivative thereof
B82Y 5/00 - Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
81.
METHODS AND SYSTEMS FOR IMAGING INTERACTIONS BETWEEN PARTICLES AND FRAGMENTS
Methods and systems for imaging interactions between particles and fragments are provided. A method includes applying a template to one or more images of a sample comprising a particle and a fragment. The template comprises a three-dimensional representation of the particle at a resolution of higher than about 1/8 reciprocal Angstroms and is produced by data independent of data provided in the one or more images. The fragment is not represented in the template. A similarity image is produced comprising a pixel-wise representation of a distance metric between the template and the one or more images. The distance metric enables detection of at least a portion of the particle or fragment. A threshold is applied to the similarity image to distinguish positive detections from noise and a representation of a volume as a function of the positive detections is produced, representing an interaction between the particle and the fragment.
A polymer nanoparticle includes a crosslinked polymer complex including a cargo encapsulated in a crosslinked polymer network; and a coating on the crosslinked polymer complex. The coating is derived from a cellular membrane. The polymer nanoparticles described herein can advantageously be used to deliver a cargo molecule (e.g., a nucleic acid) to a target location, for example upon administration to a subject in need of therapy.
Embodiments generate medical support text, e.g., assessments and plans, based on patient medical data. One such embodiment begins by receiving medical data for a given patient. Next, a patient knowledge graph for the given patient is generated based on the received medical data and an expanded graph is generated by expanding the patient knowledge graph based upon supplementary data. In turn, the medical support text for the given patient is generated based upon the expanded graph.
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
G16H 10/60 - ICT specially adapted for the handling or processing of patient-related medical or healthcare data for patient-specific data, e.g. for electronic patient records
G16H 50/70 - ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for mining of medical data, e.g. analysing previous cases of other patients
G06F 40/40 - Processing or translation of natural language
The present applications discloses an NLS-optimized SpCas9-based prime editor that improves genome editing efficiency exemplified by endogenous loci in cultured cell lines. Using this genome modification system, tumor formation can be initiated through somatic cell editing in the adult mouse. Furthermore, a dual adeno-associated vims (AAVs) is utilized for the delivery of a split-intein prime editor for correction of in vivo pathogenic mutations.
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
Aspects of the disclosure relate to compositions and methods for modulating (e.g., inhibiting or promoting) expression of certain mitochondrial regulatory proteins, for example Marf and mitofusin (Mfn). The disclosure is based, in part, on modulation of Marf or Mfn to regulate expression or activity of certain proteins involved in autophagy, for example Vmp1 and vps13D. In some embodiments, compositions and methods described by the disclosure are useful for treating diseases related to aberrant autophagy or mitochondrial function, such as familial neurological movement disorders.
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
A61K 31/712 - Nucleic acids or oligonucleotides having modified sugars, i.e. other than ribose or 2'-deoxyribose
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
87.
Use of CDK Inhibitors to Enhance Growth and Self-Renewal of Progenitor Cells
This invention relates to treating Myeloproliferative neoplasms (MPNs), specifically Polycythemia Vera (PV). In particular, the invention relates to compositions and methods for inhibiting Polycythemia Vera (PV)-initiating cells, e.g. subsets of hematopoietic stem cells that cause PV symptoms. For one example, Montelukast (e.g., Singulair®) may be used for preventing the development of PV or reducing PV symptoms over long periods of time. Further, Montelukast in combination with other compounds, e.g., JAK2 inhibitor compounds, may also find use for treating patients genetically at risk for developing PV and for PV patients.
A61K 31/519 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
A61K 31/506 - Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
A61K 31/553 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and at least one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
This disclosure relates to novel PMS1 targeting sequences. Novel PMS1 targeting oligonucleotides for the treatment of trinucleotide repeat disease or disorder are also provided. A double stranded RNA (dsRNA) molecule comprising a sense strand and an antisense strand, wherein the antisense strand comprises a sequence substantially complementary to a PMS1 nucleic acid sequence.
The present disclosure provides an engineered amphiphilic composition (for example, a lipid nanoparticle) comprising multiple CD47 proteins and at least one amphiphile. The disclosure further provides methods for enhancing the phagocytic function of macrophages by contacting the macrophages with macrophages with the engineered amphiphilic composition. The disclosure further provides methods for treating cancer by administering the engineered amphiphilic composition to a patient in need thereof.
The disclosure provides a textile having a photothermal absorber layer, which comprises a conjugated polymer; and a transmissive layer, which comprises fibers that forward scatter incident visible light with a transmission of 60% or greater. The photothermal absorber layer can be nylon coated with a conjugated polymer, such as PEDOT. The transmissive layer can be a non-woven polypropylene material. The disclosure also provides wearables, such as a clothing, comprising such textile, and methods for making the same.
D06M 23/06 - Processes in which the treating agent is dispersed in a gas, e.g. aerosols
B32B 3/28 - Layered products essentially comprising a layer with external or internal discontinuities or unevennesses, or a layer of non-planar form; Layered products essentially having particular features of form characterised by a layer with cavities or internal voids characterised by a layer comprising a deformed thin sheet, e.g. corrugated, crumpled
B32B 5/02 - Layered products characterised by the non-homogeneity or physical structure of a layer characterised by structural features of a layer comprising fibres or filaments
B32B 5/26 - Layered products characterised by the non-homogeneity or physical structure of a layer characterised by the presence of two or more layers which comprise fibres, filaments, granules, or powder, or are foamed or specifically porous one layer being a fibrous or filamentary layer another layer also being fibrous or filamentary
B32B 5/06 - Layered products characterised by the non-homogeneity or physical structure of a layer characterised by structural features of a layer comprising fibres or filaments characterised by a fibrous layer needled to another layer, e.g. of fibres, of paper
Aspects relate to patterned nanostructures having a feature size not including film thickness of below 5 microns. The patterned nanostructures are made up of nanoparticles having an average particle size of less than 100 nm. A nanoparticle composition, which, in some cases, includes a binder, is applied to a substrate. A patterned mold used in concert with electromagnetic radiation function to manipulate the nanoparticle composition in forming the patterned nanostructure. In some embodiments, the patterned mold nanoimprints a pattern onto the nanoparticle composition and the composition is cured through UV or thermal energy. Three-dimensional patterned nanostructures may be formed. A number of patterned nanostructure layers may be prepared and joined together. In some cases, a patterned nanostructure may be formed as a layer that is releasable from the substrate upon which it is initially formed. Such releasable layers may be arranged to form a three-dimensional patterned nanostructure for suitable applications.
H01B 1/08 - Conductors or conductive bodies characterised by the conductive materials; Selection of materials as conductors mainly consisting of other non-metallic substances oxides
H01B 3/10 - Insulators or insulating bodies characterised by the insulating materials; Selection of materials for their insulating or dielectric properties mainly consisting of inorganic substances metallic oxides
H01B 13/00 - Apparatus or processes specially adapted for manufacturing conductors or cables
H01M 8/124 - Fuel cells with solid electrolytes operating at high temperature, e.g. with stabilised ZrO2 electrolyte characterised by the process of manufacturing or by the material of the electrolyte
G02B 1/118 - Anti-reflection coatings having sub-optical wavelength surface structures designed to provide an enhanced transmittance, e.g. moth-eye structures
H10K 71/20 - Changing the shape of the active layer in the devices, e.g. patterning
94.
COMPOSITIONS AND METHODS FOR TREATMENT OF ACUTE LIVER FAILURE
Aspects of the disclosure relate to isolated nucleic acids encoding one or more inhibitory nucleic acids. In some embodiments, the inhibitory nucleic acids are microRNAs (miRNAs) or artificial microRNAs (amiRNAs). The inhibitory nucleic acids may target one or more genes involved in cytochrome p450 toxicity, for example Slc16a2, Acls5, and Cyb5b. In some embodiments, an inhibitory nucleic acid is a miR-375. The disclosure relates, in some aspects, to methods of reducing cytochrome p450-related toxicity in a cell (e.g., a liver cell) by administering the isolated nucleic acids of the disclosure.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
A61P 1/16 - Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
95.
DCAS13-MEDIATED THERAPEUTIC RNA BASE EDITING FOR IN VIVO GENE THERAPY
Aspects of the disclosure relate to compositions (e.g., isolated nucleic acids, rAAV vectors, rAAVs, etc.) and methods for gene editing. The disclosure is based, in part, on isolated nucleic acids encoding combinations of gene editing proteins (e.g., Cas proteins) and base editors (e.g., Adenosine Deaminase Acting on RNA deaminase domains) with certain regulatory sequences that are amenable to packaging in recombinant adeno-associated viruses (rAAVs). In some embodiments, compositions described by the disclosure are useful for treating certain diseases in a subject in need thereof.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
C12N 15/11 - DNA or RNA fragments; Modified forms thereof
e.g.,e.g., > 100 – 500 bp) DNA sequences into a target DNA sequence using a single prime editing guide RNA (pegRNA) in conjunction with a CRISPR/Cas DNA nuclease.a
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
The instant disclosure provides RNA-modulating agents that function to recruit one or more small regulatory RNA molecules (e.g., miRNA molecules, Y RNAs, and siRNAs) to a target mRNA thereby modulating (e.g., inhibiting) the translation of the target mRNA or destabilizing the mRNA. Methods for using the RNA-modulating agents are also provided.
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
C12N 15/11 - DNA or RNA fragments; Modified forms thereof
C12N 15/115 - Aptamers, i.e. nucleic acids binding a target molecule specifically and with high affinity without hybridising therewith
This disclosure relates to novel MECP2 targeting sequences. Novel MECP2 targeting oligonucleotides for the treatment of neurodegenerative diseases are also provided.
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
Protecting oligonucleotides are provided. Protecting oligonucleotides with 5' and/or 3' conjugated moieties are provided. Protecting oligonucleotides with chemical modifications are provided. Methods of using the protecting oligonucleotides for genome editing with a CRISPR nuclease and kits for performing the same are also provided. Wherein a protecting oligonucleotide comprises: (a) a sequence that is complementary to a crRNA; and (b) at least one chemically modified nucleotide.
Aspects of the disclosure relate to compositions and methods for expressing anti-Vascular endothelial cell growth factor (VEGF) agent in a cell or subject. In some embodiments, the disclosure provides rAAVs comprising a capsid protein (e.g., AAV2 variants, AAV2/3 hybrid variants, AAV8 variants, etc.), and a transgene encoding an anti-VEGF agent (e.g., KH902) and one or more regulatory sequences. In some embodiments, compositions described herein are useful for treating subjects having diseases associated with angiogenesis or aberrant VEGF activity/signaling.
