The present invention is related to compositions and methods for gene therapy. Several approaches described herein utilize the Neisseria meningitidis Cas9 system that provides a hyperaccurate CRISPR gene editing platform. Furthermore, the invention incorporates full length and truncated single guide RNA sequences that permit a complete sgRNA-Nme1Cas9 vector to be inserted into an adeno-associated viral plasmid that is compatible for in vivo administration. Furthermore, Type II-C Cas9 orthologs have been identified that target protospacer adjacent motif sequences limited to between one-four required nucleotides.
A composition includes particular amounts of a first solvent selected from benzaldehyde, 1,3-dioxolane, tetrahydropy-ran, 4-picoline, ethyl benzoate, methyl benzoate, or a combination thereof; a second solvent selected from cyclic ketones, aliphatic ketones, methyl acetate, dimethyl carbonate, tert-butyl acetate, propylene carbonate, PCBTF, ethyl acetate, 1,2-butylene oxide, anisole, dimethyl acetamide (DMA), pyridine, dimethyl maleate, dimethyl sulfide, triethyl phosphate, pyrrolidine, 1-vinyl-2-pyrrolidinone, 2-pyrrolidinone, thioacetic acid, N, N diethyl formamide, n-methyl pyrrole, 2-methyl pyrazine, ethyl iodide, dimethyl sulfoxide (DMSO), or a combination thereof. The solvent composition can be particularly useful in adhesive formulations such as solvent cements.
C09J 5/02 - Adhesive processes in generalAdhesive processes not provided for elsewhere, e.g. relating to primers involving pretreatment of the surfaces to be joined
C08J 5/12 - Bonding of a preformed macromolecular material to the same or other solid material such as metal, glass, leather, e.g. using adhesives
C09J 127/06 - Homopolymers or copolymers of vinyl chloride
Lane segment-level traversal information is obtained. The lane segment-level traversal information is converted into probabilities for a state transition function. A policy is derived from a decision model using the state transition function. The policy directs vehicle movement of a vehicle between neighboring lane segments based on a cost function integrating a user preference with respect to at least two objectives and a slack time for alternative routes. The slack time indicates an allowable deviation in travel time relative to the user preference. A destination is received. The vehicle is then autonomously controlled on a route to the destination using the policy for lane transitions based on current lane positions.
Ageratum plant named ‘Agerboyuma’, characterized by its relatively compact, upright to outwardly spreading and mounding plant habit; moderately vigorous to vigorous growth habit; freely branching habit; relatively large leaves; freely and continuous flowering habit; light violet-colored inflorescences that resist fading; and good garden performance.
The invention provides novel hybrid polystyrene (PS)/poly(lactic-co-glycolic acid) (PLGA) core-shell microbeads having viscous surface coating and heterogeneous size distribution, and methods of their preparation and use in animal models.
The present invention is related to compositions and methods for gene therapy. Several approaches described herein utilize the Neisseria meningitidis Cas9 system that provides a hyperaccurate CRISPR gene editing platform. Furthermore, the invention incorporates full length and truncated single guide RNA sequences that permit a complete sgRNA-Nme1Cas9 vector to be inserted into an adeno-associated viral plasmid that is compatible for in vivo administration. Furthermore, Type II-C Cas9 orthologs have been identified that target protospacer adjacent motif sequences limited to between one-four required nucleotides.
Device and methods for treating wounds or surgical sites are provided. The devices and methods include use of antifibrinolytic agents such as tranexamic acid to reduce exudate and improve wound healing. Embodiments provide for the timed release of therapeutic agents from wound dressings to extend a delivery time through the inflammatory phase of wound healing.
A61K 31/196 - Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
A61L 15/64 - Use of materials characterised by their function or physical properties specially adapted to be resorbable inside the body
A61L 26/00 - Chemical aspects of, or use of materials for, liquid bandages
A61L 27/54 - Biologically active materials, e.g. therapeutic substances
A61L 27/58 - Materials at least partially resorbable by the body
9.
ANTIGEN DELIVERING SALMONELLA FOR USE AS A TUMOR HOMING BEACON TO REFOCUS PREEXISTING, VACCINE GENERATED T CELLS TO COMBAT CANCER
To make an immunotherapy that is effective for a larger group of cancer patients, Salmonella have been genetically engineered to deliver proteins from prior vaccines into the cytoplasm of tumor cells.
Provided herein are self-delivering oligonucleotides that are characterized by efficient RISC entry, minimum immune response and off-target effects, efficient cellular uptake without formulation, and efficient and specific tissue distribution.
In some aspects, the disclosure relates to methods for improving titer and yield of viral vector production. In some embodiments, the disclosure relates to compositions and methods of using same, wherein the compositions comprise (i) a cis-element nucleic acid comprising a transgene: (ii) a helper nucleic acid encoding adenoviral helper genes; and (iii) a packaging nucleic acid encoding Rep and/or Cap genes: wherein the ratio of (i): (ii) and/or the ratio of (i): (iii) is between 0.01:1 and 0.1:1.
Provided herein are methods and compositions for treating cancer. One composition includes an engineered bacterial cell comprising: a) a lysis gene or lysis cassette operably linked to an intracellularly induced Salmonella promoter; b) one or more of the bacterial cell genes selected from the group consisting of recA, recB, recF, sbcB, sbcCD, red, sseJ or any combination thereof are knocked out; and c) a nucleic acid sequence coding for an oncolytic virus genome.
The invention provides novel triplet-triplet annihilation upconversion nanoparticles as background free self-standing biological sensors, and devices and methods thereof.
C12Q 1/26 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving oxidoreductase
C09K 11/02 - Use of particular materials as binders, particle coatings or suspension media therefor
C12Q 1/54 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving glucose or galactose
G01N 33/543 - ImmunoassayBiospecific binding assayMaterials therefor with an insoluble carrier for immobilising immunochemicals
14.
COMPOSITIONS AND METHODS FOR THE TREATMENT OF EXPANDED REPEAT-ASSOCIATED DISORDERS
Translation modulating agents that modulate expression of one or more translation start sites for expanded repeat (e.g., DPR) protein synthesis are provided. Compositions and methods for treating translation start sites for expanded repeat (e.g., DPR) protein synthesis-associated disorders are also provided.
A61K 31/7105 - Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
A61K 31/7088 - Compounds having three or more nucleosides or nucleotides
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 31/7115 - Nucleic acids or oligonucleotides having modified bases, i.e. other than adenine, guanine, cytosine, uracil or thymine
A61K 31/712 - Nucleic acids or oligonucleotides having modified sugars, i.e. other than ribose or 2'-deoxyribose
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
Provided herein are antimicrobial microcin peptides and genetically engineered microorganisms expressing the peptides, and compositions comprising the peptides and microorganisms for treating or reducing the risk of dysbiosis or bacterial infections in animals or plants, and further discloses methods of making and using such microorganisms.
Described herein are compositions and methods for use in targeting neuropilin 2 (NRP2) in lethal prostate cancer, e.g., in metastatic castration-resistant prostate cancer (mCRPC) or neuroendocrine prostate cancer (NEPC).
A61K 38/17 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from animalsPeptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from humans
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
A61P 35/04 - Antineoplastic agents specific for metastasis
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
G01N 33/573 - ImmunoassayBiospecific binding assayMaterials therefor for enzymes or isoenzymes
G01N 33/574 - ImmunoassayBiospecific binding assayMaterials therefor for cancer
Aspects of the disclosure relate to compositions, such as rAAV vectors, comprising one or more short hairpin nucleic acids positioned outside of the inverted terminal repeats (ITRs) of the rAAV vector (referred to in some embodiments as “stopper DNA”). The disclosure is based, in part, on rAAV vectors comprising stopper DNA, which have improved packaging and/or immunogenicity relative to previously described rAAV vectors. In some embodiments, the disclosure relates to methods of delivering a transgene to a subject comprising administering the rAAV vectors.
Roller pumps are described for processing polymer, food, and other materials wherein the feedstock may contain a variety of solids and liquids, including mixtures thereof, and at a variety of temperature, pressures, and flow rates. Each roller pump apparatus includes a series dynamically formed entrapped volumes that become progressively smaller from its inlet to its outlet. The dynamically formed entrapped volumes are designed to allow unprocessed material to be reprocessed. Pumps may be designed with balanced or unbalanced rotors, and multiple pump stages can be defined with progressively smaller volumes and tighter clearances to efficiently process material with increasing density and pressure. A roller pump design is also described that is used with a feed screw to provide positive displacement control suitable for use in extrusion, molding, and other material processing applications.
In some aspects, the disclosure relates to compositions and methods for modulating (e.g., increasing and/or decreasing) bone mass in a subject. In some aspects, the disclosure provides isolated nucleic acids, and vectors such as rAAV vectors, configured to express transgenes that promote (e.g., increase) or inhibit (e.g., decrease) activity, differentiation, or function of certain types of bone cells, for example osteoblasts, osteoclasts, osteocytes, etc. In some embodiments, the isolated nucleic acids and vectors described by the disclosure are useful for treating disorders and conditions associated with increased bone mass (e.g., osteopetrosis) or decreased bone mass (e.g., osteoporosis).
The invention relates to chemically reactive and/or biologically active compounds, reagents and compositions thereof. More particularly, the invention provides novel reagents that are useful in chemical synthesis, functionalization, delivery, probing and/or analytical measurements of small molecule drugs, proteins, antibodies and other biomolecules. The invention provides novel biologically active agents useful as diagnostics or therapeutics, and related composition and methods of uses thereof.
C07C 69/736 - Ethers the hydroxy group of the ester being etherified with a hydroxy compound having the hydroxy group bound to a carbon atom of a six-membered aromatic ring
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
C07C 69/593 - Dicarboxylic acid esters having only one carbon-to-carbon double bond
C07C 229/30 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and unsaturated
C07C 229/34 - Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
C07C 235/28 - Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and unsaturated
C07C 271/28 - Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring to a carbon atom of a non-condensed six-membered aromatic ring
C07C 311/53 - X and Y not being nitrogen atoms, e.g. N-sulfonylcarbamic acid
C07C 323/54 - Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and unsaturated
Compositions and methods for treating or reducing the severity of occurrence of a parasitic worm or helminth infection in a subject are described. The methods include administering to the subject a therapeutically effective amount of a composition comprising isolated native, bioactive nematicidal crystals formed from a single type of nematicidal crystal protein. The isolated native, bioactive nematicidal crystals are substantially free of any bacterial spores or host bacterial proteins, other than nematicidal crystal protein in the form of a crystal. Methods for making isolated native, bioactive nematicidal crystals are also described. The crystal proteins may be full length, truncated, variant, or sub-variant Cry proteins. Examples of crystal proteins include Cry5B, Cry21, Cry14A, Cry6A, and Cry13A.
Methods for treating inflammatory skin diseases involving inhibition of solute carrier family 46 member 2 (SLC46A2) and/or solute carrier family 46 member 3 (SLC46A3).
An acidified oleogel composition includes particular amounts of an organic acid, water, a surfactant, and an oil-structuring agent. The acidified oleogel can be used to provide water-in-oil emulsions, which can be particularly useful in the sanitization of various surfaces including food-contacting surfaces.
A01N 25/30 - Biocides, pest repellants or attractants, or plant growth regulators, characterised by their forms, or by their non-active ingredients or by their methods of applicationSubstances for reducing the noxious effect of the active ingredients to organisms other than pests characterised by the surfactants
A01P 1/00 - DisinfectantsAntimicrobial compounds or mixtures thereof
24.
LASER DIODE BEAM CORRECTION, COMBINING, AND COUPLING USING METALENS DOUBLETS
The present disclosure provides systems and methods for coupling light in imaging systems. One such system comprises a metalens doublet structure having a first substrate; a first metalens structure provided at a surface of the first substrate and comprising a plurality of first scatterers; and a second metalens structure provided at a second substrate or on another surface of the first substrate and comprising a plurality of second scatterers. Accordingly, the plurality of first scatterers is configured to reshape the intensity distribution of light that is received by the first metalens structure at a location of the second metalens structure; and the plurality of second scatterers is configured to change a wavefront of the light outputted from the first metalens structure and incident on the second metalens structure.
G02B 3/08 - Simple or compound lenses with non-spherical faces with discontinuous faces, e.g. Fresnel lens
G02B 1/00 - Optical elements characterised by the material of which they are madeOptical coatings for optical elements
G02B 6/12 - Light guidesStructural details of arrangements comprising light guides and other optical elements, e.g. couplings of the optical waveguide type of the integrated circuit kind
G02B 6/122 - Basic optical elements, e.g. light-guiding paths
G02B 27/09 - Beam shaping, e.g. changing the cross-sectioned area, not otherwise provided for
The present invention relates to a negative pressure wound closure system and methods for using such a system. Preferred embodiments of the invention facilitate closure of the wound by preferentially contracting to provide for movement of the tissue. Preferred embodiments can utilize tissue securing portions that aid in securing the invention within a wound.
A61F 13/05 - Bandages or dressingsAbsorbent pads specially adapted for use with sub-pressure or over-pressure therapy, wound drainage or wound irrigation, e.g. for use with negative-pressure wound therapy [NPWT]
A61M 1/00 - Suction or pumping devices for medical purposesDevices for carrying-off, for treatment of, or for carrying-over, body-liquidsDrainage systems
Aspects of the disclosure relate to compositions and methods for expressing adeno- associated virus capsid proteins. The disclosure relates, in part, to novel synthetic AAV vectors comprising a Rep gene positioned upstream of a 5' inverted terminal repeat (ITR), a promoter operably linked to a capsid protein-encoding nucleic acid sequence. Methods of producing an rAAV capsid library are also disclosed.
Use of high frequency waves, such a millimeter waves, in many circumstances is prevented due to their inability to diffract around common obstacles. Disclosed herein is a system and method for transforming an incident high frequency wave. The system includes meta-atom pairs that define a surface. The meta-atom pairs generate an electro-magnetic response by interacting with an incident wave. This electro-magnetic response can be modulated by applying voltage to the meta-atom pairs. The electro-magnetic response transforms the incident wave into an emitted wave based on its controlled properties. The system and method are able to, by changing the voltage applied, steer the emitted wave a full 360 degrees as wells as transmit it through the surface without significant power loss. Embodiments enable the transmission through or around many obstacles that would normally interfere with high frequency waves.
A method of forming a convertible ink. The method includes: performing a polyol process with a metal salt, a capping agent and a solvent to produce encapsulated nanospheres in a first aqueous solution; reducing the amount of capping agent in the solution. The capping agent can be reduced by: adding solvent soluble with the capping agent and agitating the mixture via centrifugation to form a supernatant and a precipitate that includes the encapsulated nanospheres; removing the supernatant; adding a second solvent to the precipitate to form a second solution; agitating the second solution to form a second supernatant and a precipitate that includes the encapsulated nanospheres; and removing the second supernatant.
Disclosed herein are methods for assessing RNA contamination (purity) and integrity. The present disclosure provides methods of detecting defective, unwanted, undesirable, and/or unexceptional ribonucleic acids (RNAs). The present disclosure also provides methods of measuring quantity and/or quality of an RNA. The present disclosure also provides methods validating a personalized therapeutic composition comprising an RNA.
C12Q 1/689 - Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for detection or identification of organisms for bacteria
Hematopoietic stem cells (HSC) are essential to developing a functional immune system, including monocyte-macrophage cells required for wound healing. Described herein are methods of using yellow bone marrow as a source of cells to generate hematopoietic stem cells. The methods include expansion of human hematopoietic stem cells by culture of human yellow bone marrow in 3-dimensional hydrogel and pro-angiogenic, stem cell-promoting medium.
The disclosure relates to compositions, systems, and methods comprising ethylene glycol chemical modifications on oligonucleotides to modulate silencing activity and improve stability.
In some aspects, the disclosure relates methods for treating ventricular tachycardia in a subject. In some embodiments, methods of the disclosure comprise measuring action potential durations and/or expression levels of KCNE3 and/or KCNE4 in a subject. In some aspects, the disclosure relates to methods and compositions for reducing or inhibiting the activity of KCNE3 and/or KCNE4, for example, in subjects having ventricular tachycardia.
A method of forming a convertible ink. The method includes: performing a polyol process with a metal salt, a capping agent and a solvent to produce encapsulated nanospheres in a first aqueous solution; reducing the amount of capping agent in the solution. The capping agent can be reduced by: adding solvent soluble with the capping agent and agitating the mixture via centrifugation to form a supernatant and a precipitate that includes the encapsulated nanospheres; removing the supernatant; adding a second solvent to the precipitate to form a second solution; agitating the second solution to form a second supernatant and a precipitate that includes the encapsulated nanospheres; and removing the second supernatant.
In some aspects the disclosure provides compositions and methods for promoting expression of functional NEU1 protein in a subject. In other aspects, the disclosure provides compositions and methods for treating sialidosis, galactosialidosis, and/or Alzheimer's Disease in a subject having or suspected of having sialidosis, galactosialidosis, and/or Alzheimer's Disease.
Aspects of the disclosure relate to compositions and methods for reducing expression or activity of superoxide dismutase 1 (SOD1) in a cell or subject. In some embodiments, the compositions, such as nucleic acid and viral vectors, comprise artificial microRNAs (amiRNAs) having a SOD 1 -targeting sequence positioned within a microRNA scaffold. In some embodiments, the compositions further comprise a human SMN1 promoter. In some aspects, the methods comprise administering a composition of the disclosure to a subject, for example a subject having amyotrophic lateral sclerosis (ALS).
The disclosure relates to compositions, systems, and methods comprising ethylene glycol chemical modifications on oligonucleotides to modulate silencing activity and improve stability.
The present disclosure provides, in some aspects, a humanized immunodeficient mouse model of human fibrosis. A humanized immunodeficient mouse model provided herein may be used, for example, for modeling human fibrosis, predicting human fibrosis, and testing putative fibrosis treatments.
Provided herein are methods of treating cancer in a subject that include administering to the subject a therapeutically effective amount of an inhibitor of UXS1, wherein the inhibitor of UXS1 comprises an inhibitory nucleic acid, and wherein the subject is diagnosed as having a UDGH-high cancer, thereby treating the UDGH-high cancer.
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
40.
NANOPORE-MATCHED PROTEIN SHUTTLE FOR MOLECULAR CHARACTERIZATION
Systems and methods are provided for trapping and electrically monitoring molecules in a nanopore sensor. The nanopore sensor comprises a support structure with a first and a second fluidic chamber, at least one nanopore fluidically connected to the two chambers, and a protein shuttle. The protein shuttle comprises an electrically charged protein molecule, such as Avidin. The nanopore can be a Clytosolin A. A method can comprise applying a voltage across the nanopores to draw protein shuttles towards the nanopores. The ionic current through each or all of the nanopores can be concurrently measured. Based on the measured ionic current, blockage events can be detected. Each blockage event indicates a capture of a protein shuttle by at least one nanopore. Each blockage event can be detected through a change of the total ionic current flow or a change in the ionic current flow for a particular nanopore.
Triazole-containing deoxybenzoin compounds are described herein. The compounds can exhibit a desirable range of thermal properties pertaining to low heat release and low flammability. In a further advantageous feature, the compounds can be used to provide triazole-containing deoxybenzoin polymers.
An impact protecting device includes flocked energy absorbing material (FEAM) impact force absorbing (IFA) segments. Each segment includes a double-sided flock section; a segment cover disposed covering the double-sided flock section and an outer elastic cover enclosing the plurality of FEAM IFA segments including stitching to keep the segments adjacent to adjoining segments but separated. The device further includes overlapped segments to provide extra head protection for the forehead and frontal head areas.
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
A61K 31/343 - Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
A61K 31/397 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having four-membered rings, e.g. azetidine
A61K 31/4025 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
A61K 31/4184 - 1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
A61K 31/4525 - Non-condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
A61K 31/5377 - 1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
C07D 307/93 - Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems condensed with a ring other than six-membered
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 405/10 - 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
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
The disclosure herein provides, in example embodiments, methods of treating a subject in need thereof, e.g., a subject with polycystic kidney disease (PKD), for example, with an antibody-drug conjugate comprising, e.g., tumor-associated calcium signal transducer 2 protein (TACSTD2).
A61K 47/68 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
A61K 31/55 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
A61P 13/12 - Drugs for disorders of the urinary system of the kidneys
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
A61K 31/395 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
C07D 307/77 - Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
C07D 307/93 - Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems condensed with a ring other than six-membered
C07D 493/02 - Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
An optical probe includes a probe body and a shank extending from the probe body to a tip. The tip includes a first plurality of light emitting diode pixels and a first plurality of recording electrodes. The first plurality of light emitting diode pixels includes a first light emitting diode and a second light emitting diode, wherein the first light emitting diode and the second light emitting diode emit a different color of light. The first plurality of light emitting diode pixels are arranged in groups. The light emitting diode pixels and groups of pixels are arranged in a particular manner. Methods for the manufacture of the probe and methods of using the probe are also described.
Provided is an RNA vector comprising: a permuted group 1 intron/exon comprising a 5' exon, a 3' exon, and an intron, the intron comprising a 5' intron end and a 3' intron end; and at least one modified nucleotide; wherein the 3' exon is upstream of the 5' exon; wherein a portion of the intron including the 3' intron end is upstream of the 3' exon; wherein a portion of the intron including the 5' intron end is downstream of the 5' exon; and wherein the permuted group 1 intron/exon is active in the presence of the modified nucleotide. Also provided is a DNA vector and methods for expressing a target protein from a circular RNA vector.
Disclosed herein is a fluid composition for depolymerizing a polymer comprising 5 to 90 volume percent of carbon dioxide in supercritical fluid form; 5 to 90 volume percent of superheated water; and 5 to 90 volume percent of an alcohol; where the alcohol is in either its superheated state or supercritical fluid; where all volume percents are based on a total volume of the fluid composition; where the fluid composition is at a temperature greater than 150°C, a pressure greater than 500 psi for a time period greater than 30 minutes.
C08J 11/10 - Recovery or working-up of waste materials of polymers by chemically breaking down the molecular chains of polymers or breaking of crosslinks, e.g. devulcanisation
C08J 11/24 - Recovery or working-up of waste materials of polymers by chemically breaking down the molecular chains of polymers or breaking of crosslinks, e.g. devulcanisation by treatment with organic material by treatment with organic oxygen-containing compounds containing hydroxyl groups
C08J 11/04 - Recovery or working-up of waste materials of polymers
50.
COMPOSITION FOR DEPOLYMERIZING RESINS AND METHODS OF ACCOMPLISHING THE SAME
Disclosed herein is a method of solubilizing a polymeric resin comprising treating the polymeric resin or a composite comprising the polymeric resin with a first mixture of fluids for one or more pressure cycles; where the first mixture comprises a first superheated fluid and a first supercritical fluid; where each pressure cycle comprises a pressurization step, a pressure retention step and a depressurization step; and treating the polymeric resin or the composite comprising the polymeric resin to one or more pressure cycles with a second mixture of fluids; where the second mixture of fluids comprises superheated water, a second superheated or supercritical fluid and a third supercritical fluid; where the first superheated fluid and the second superheated or supercritical fluid comprise a solvent has a Hildebrand solubility parameter between 15 and 40 (MPa)1/2.
C08G 18/00 - Polymeric products of isocyanates or isothiocyanates
B32B 5/24 - 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
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
The present disclosure provides oligonucleotides, methods, and compositions for degrading RNA via the lysosomal pathway. Also contemplated are oligonucleotides, methods, and compositions for the treatment, prevention, or amelioration of diseases, disorders, and conditions associated with EXOC2, Ku80, and Task1 in a subject in need thereof.
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 device may include a porous substrate. A device may include a superhydrophobic coating applied to at least a portion of the porous substrate. A device may include a gas source adapted to deliver gas through the porous substrate and to contact the superhydrophobic coating.
The present disclosure relates to chimeric human papillomavirus (HPV) compositions for use in preventing infectious diseases. The present disclosure also relates to methods of generating chimeric HPV compositions using transgenic plant methods.
C12N 7/00 - Viruses, e.g. bacteriophagesCompositions thereofPreparation or purification thereof
C07K 14/025 - Papovaviridae, e.g. papillomavirus, polyomavirus, SV40, BK virus, JC virus
C07K 14/22 - Peptides having more than 20 amino acidsGastrinsSomatostatinsMelanotropinsDerivatives thereof from bacteria from Neisseriaceae (F), e.g. Acinetobacter
C12N 15/62 - DNA sequences coding for fusion proteins
Disclosed are compositions comprising genomic safe harbor (GSH) loci and methods using same. Further disclosed are methods of identifying novel GSH loci.
This disclosure relates to oligonucleotides with internucleotide linkage modifications and used thereof for treating and preventing kidney diseases. In particular, the present disclosure provides compositions, systems, and methods for the delivery of therapeutic oligonucleotide to kidney. The oligonucleotide disclosed herein can be delivered to the kidney upon administration.
The present invention provides a Cas9 platform to facilitate single-site nuclease gene editing precision within a human genome. For example, a Cas9 nuclease/DNA-targeting unit (Cas9-DTU) fusion protein precisely delivers a Cas9/sgRNA complex to a specific target site within the genome for subsequent sgRNA-dependent cleavage of an adjacent target sequence. Alternatively, attenuating Cas9 binding using mutations to the a protospacer adjacent motif (PAM) recognition domain makes Cas9 target site recognition dependent on the associated DTU, all while retaining Cas9's sgRNA-mediated DNA cleavage fidelity. Cas9-DTU fusion proteins have improved target site binding precision, greater nuclease activity, and a broader sequence targeting range than standard Cas9 systems. Existing Cas9 or sgRNA variants (e.g., truncated sgRNAs (tru-gRNAs), nickases and FokI fusions) are compatible with these improvements to further reduce off-target cleavage. A robust, broadly applicable strategy is disclosed to impart Cas9 genome-editing systems with the single-genomic-site accuracy needed for safe, effective clinical application.
Various examples disclosed relate to a method of manufacturing a mechanically stabilized material that includes a nanostructure. The method includes providing a curable material disposed on a substrate. The curable material includes inorganic nanoparticles. The method further includes exposing the curable material and the substrate to pulsed electromagnetic radiation to form the mechanically stabilized material.
G03F 7/00 - Photomechanical, e.g. photolithographic, production of textured or patterned surfaces, e.g. printed surfacesMaterials therefor, e.g. comprising photoresistsApparatus specially adapted therefor
Provided herein, in various embodiments, are methods of diagnosing a subject as having, or having a propensity to develop, a fragile X-associated disorder (e.g., FXS), methods of prognosing a fragile X-associated disorder (e.g., FXS) in a subject, methods of predicting a treatment outcome of a fragile X-associated disorder (e.g., FXS) in a subject, methods of stratifying a set of subjects having a fragile X-associated disorder, methods of stratifying a population of subjects having, or having a propensity to develop, FXS, and method for assessing the efficacy of a drug for treatment of FXS. Also provided herein, in various embodiments, are assays and systems useful for performing the disclosed methods. The present disclosure also provides methods of treating a subject having FXS.
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
This disclosure relates to oligonucleotides with internucleotide linkage modifications and used thereof for treating and preventing diseases. Particularly, this disclosure relates to SLC5A2 targeting sequences, and methods for treating and preventing kidney diseases using same.
Provided herein are methods and compositions for treating cancer by contacting cancer cells with a CRISPR nickase and a single guide RNA (sgRNA) targeting at least one sequence in the cancer cells.
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
C12N 15/10 - Processes for the isolation, preparation or purification of DNA or RNA
64.
FORMULATIONS FOR FORMING A STRUCTURED NANOPARTICLE COMPOSITE
Structured nanoparticle composite and methods and formulations for forming the same. A formulation for forming a structured nanoparticle composite includes a nanoparticle with an average diameter of less than 50 nm. The formulation includes at least one solvent with a boiling point of 40° C. to 300° C. The formulation includes a binder for the nanoparticles that is the solvent or that has a different chemical structure than the solvent.
G03F 7/00 - Photomechanical, e.g. photolithographic, production of textured or patterned surfaces, e.g. printed surfacesMaterials therefor, e.g. comprising photoresistsApparatus specially adapted therefor
C09D 11/033 - Printing inks characterised by features other than the chemical nature of the binder characterised by the solvent
C09D 11/101 - Inks specially adapted for printing processes involving curing by wave energy or particle radiation, e.g. with UV-curing following the printing
Provided herein are self-delivering oligonucleotides that are characterized by efficient RISC entry, minimum immune response and off-target effects, efficient cellular uptake without formulation, and efficient and specific tissue distribution.
C12N 15/11 - DNA or RNA fragmentsModified forms thereof
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
A61K 47/61 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule the organic macromolecular compound being a polysaccharide or a derivative thereof
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
The present application provides compounds useful in treating various inflammatory disease and conditions, for example, various PAD and/or STING-associated disorders.
A61K 31/4453 - Non-condensed piperidines, e.g. piperocaine only substituted in position 1, e.g. propipocaine, diperodon
C07C 251/08 - Compounds containing nitrogen atoms doubly- bound to a carbon skeleton containing imino groups having carbon atoms of imino groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of a saturated carbon skeleton being acyclic
C07D 209/46 - Iso-indolesHydrogenated iso-indoles with an oxygen atom in position 1
C07D 235/14 - Radicals substituted by nitrogen atoms
C07D 249/06 - 1,2,3-TriazolesHydrogenated 1,2,3-triazoles with aryl radicals directly attached to ring atoms
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 3/10 - Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
A61P 9/10 - Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
A61P 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
68.
A-REPEAT MINIGENE COMPOSITIONS FOR TARGETED REPRESSION OF SELECTED CHROMOSOMAL REGIONS AND METHODS OF USE THEREOF
This invention relates to compositions and methods for modulating gene expression, e.g., allele-specific gene expression, and to DNA sequences that can be integrated into targeted genomic locations (e.g., introns, exons, non-coding regions) within or near one or more alleles and confer reduced expression of said allele(s). Targeted alleles include, but are not limited to, gene sequences, translocated sequences, fully or partially duplicated sequences, and integrated viral-derived sequences.
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
This disclosure relates to novel SNCA targeting sequences. Novel SNCA 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
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
A61K 47/55 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound 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
A61K 48/00 - Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseasesGene therapy
70.
IMPROVED MODULAR PRIME EDITING WITH MODIFIED EFFECTORS AND TEMPLATES
Provided are modular prime editing systems, comprising: i) a fusion protein comprising a Cas9 nickase protein linked to a nucleotide polymerase (NT) protein, ii) a prime editor template RNA (petRNA) comprising a primer binding site (PBS), a nucleotide polymerase template (NPT), and at least one MS2 hairpin, and iii) a single guide RNA (sgRNA).
Aspects of the disclosure relate to barcoded chimeric adeno-associated virus (AAV) capsid libraries, chimeric capsids and related recombinant AAVs (rAAVs) identified using the libraries. Specifically, the chimeric AAV capsid libraries comprise a plurality of nucleic adds encoding AAV capsid proteins, wherein each nucleic acid (i) encodes a unique AAV capsid protein having distinct polypeptide regions of greater than six amino acids in length that are derived from at least two different AAV serotypes, and (ii) comprises a unique barcode sequence. Further disclosed are methods of preparing an AAV library and identifying AAV capsids tropic for a target tissue.
Some aspects of the disclosure provide truncated potassium voltage-gated channel subfamily H member 2 (KCNH2) proteins. In some aspects, the disclosure provides nucleic acid regulatory elements comprising (i) an atrial natriuretic peptide (Anf) promoter and (ii) an enhancer element, wherein the enhancer element is not a naturally-occurring Anf enhancer element.
This disclosure relates to the combination of DGAT2 targeting sequences with FASN, OPN, and/or NOX4 targeting sequences, and methods for treating and preventing non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and lipodystrophy syndromes.
Provided herein are compounds of Formulae (I) and (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. Also provided are methods, uses, and kits involving the disclosed compounds and pharmaceutical compositions thereof for treating and/or preventing a disease (e.g., a metabolic disorder (e.g., obesity, diabetes), a hypoxia related disease (e.g., a proliferative disease, inflammatory disease, neuromuscular disorder, neurodegenerative disorder, hypoxia, ischemia, oxidative stress, or a mitochondrial DNA related disorder), or a disease resulting from rhodoquinone depletion (e.g., a proliferative disease, inflammatory disease, neuromuscular disorder, metabolic disorder, or neurodegenerative disorder)) in a subject.
Provided herein are compounds of Formulae (I) and (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. Also provided are methods, uses, and kits involving the disclosed compounds and pharmaceutical compositions thereof for treating and/or preventing a disease (e.g., a metabolic disorder (e.g., obesity, diabetes), a hypoxia related disease (e.g., a proliferative disease, inflammatory disease, neuromuscular disorder, neurodegenerative disorder, hypoxia, ischemia, oxidative stress, or a mitochondrial DNA related disorder), or a disease resulting from rhodoquinone depletion (e.g., a proliferative disease, inflammatory disease, neuromuscular disorder, metabolic disorder, or neurodegenerative disorder)) in a subject.
A61K 31/136 - Amines, e.g. amantadine having aromatic rings, e.g. methadone having the amino group directly attached to the aromatic ring, e.g. benzeneamine
A61K 45/06 - Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
75.
HOXA11AS LONG NON-CODING RNA IN INFLAMMATORY BOWEL DISEASE
Provided herein are gene replacement approaches to restore HOXA11AS in the colon for patients with IBD, e.g., UC. Further, since HOXA11os levels inversely correlate with disease severity this lncRNA can also be used as a sensitive colon specific disease relevant biomarker.
A cured product of a liquid complex coacervate includes a macroion phase of a polyanion, a polycation, and a salt; wherein the polyanion has repeating units including one or more of a carboxylate group, a sulfonate group, a phosphonate group, a sulfate group, or a phosphate group; and wherein the polycation has repeating units including one or more of a nitrogen-containing cationic group, a phosphorus-containing cationic group, or a sulfur-containing cationic group; provided that when the polycation is poly(diallyldimethyl ammonium), the poly anion is not polystyrene sulfonate, or when the polyanion is polystyrene sulfonate, the polycation is not poly(diallyldimethyl ammonium). Methods of forming coatings are also disclosed.
An approach for determining regulatory status of water resources under the Clean Water Act includes receiving input data layers for a geographic location, preprocessing the layers into a multi-channel image, feeding the image into a trained convolutional neural network, obtaining an output score indicating a probability of regulated waters, and determining regulatory status based on the score. The input layers may include aerial imagery, wetland/stream data, soil/elevation/climate data, land cover classification, and regulatory boundary data. The neural network may be trained on approved jurisdictional determinations. The method enables efficient, consistent predictions of Clean Water Act jurisdiction across diverse water resources and geographic regions. By incorporating regulatory information alongside environmental data, the approach accounts for variations in Clean Water Act implementation across jurisdictions and regulatory regimes. The scalable method supports rapid evaluation of large areas for policy analysis and environmental planning.
Aspects of the disclosure relate to compositions and methods for treating spinal muscular atrophy (SMA). The disclosure is based, in part, on isolated nucleic acids and vectors (e.g., viral vectors, such as rAAV vectors) encoding SMN1. In some embodiments, the expression of SMN 1 is driven by a native SMN 1 promoter or a variant thereof. In some embodiments, isolated nucleic acids and vectors of the disclosure have reduced toxicity and/or increased transgene expression relative to previously described SMN-encoding vectors.
A transmission line as discussed herein includes: an input node operative to receive input derived from a primary signal and a pump signal; an output node operative to output an output signal; and circuitry disposed in a circuit path extending between the input node and the output node, the circuitry including a first Josephson junction component coupled between the circuit path and a reference voltage node, the circuitry operative to amplify the primary signal to produce the output signal.
H01P 3/00 - WaveguidesTransmission lines of the waveguide type
H03K 17/92 - Electronic switching or gating, i.e. not by contact-making and -breaking characterised by the use of specified components by the use, as active elements, of superconductive devices
This disclosure relates to oligonucleotides with internucleotide linkage modifications and used thereof for treating and preventing kidney diseases. In particular, the present disclosure provides compositions, systems, and methods for the delivery of therapeutic oligonucleotide to kidney. The oligonucleotide disclosed herein can be delivered to the kidney upon administration.
C07H 19/067 - Pyrimidine radicals with ribosyl as the saccharide radical
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
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
82.
BIOMARKERS AND METHODS RELATED TO FRAGILE X SYNDROME
Provided herein, in various embodiments, are methods of treating fragile X syndrome (FXS), comprising determining in a sample from the subject: a presence, an absence, or a level of an FXS-associated metabolite; an alteration or a ratio of a level of an FXS-associated metabolite, relative to a reference level of the same metabolite; a ratio between levels of two FXS-associated metabolites, or an alteration thereof relative to a reference ratio of the two FXS- associated metabolites, or a combination of the foregoing. Also provided herein, in various embodiments, are methods of diagnosing, prognosing, subclassifying and/or predicting a treatment outcome of FXS in a 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
A61K 39/395 - AntibodiesImmunoglobulinsImmune serum, e.g. antilymphocytic serum
A61P 25/00 - Drugs for disorders of the nervous system
A61P 25/14 - Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
83.
AMPLIFIABLE METABOLIC LABELING FOR DETECTION OF BACTERIAL VIABILITY, GROWTH AND ANTIBIOTIC SUSCEPTIBILITY
Provided herein is a rapid amplifiable readout of bacterial growth, such as an ELISA paired with metabolic labeling. Methods comprise a) contacting a sample from a subject suffering from a bacterial infection with an antibiotic; and b) determining the effect, if any, of the antibiotic on incorporation of a single- or di-D-amino acid into peptidoglycan of the bacterial cell or incorporation of trehalose into the bacterial cell envelope, wherein an antibiotic that reduces, as compared to control without the antibiotic being present, incorporation of the D-amino acid into peptidoglycan of the bacterial cell or inhibited incorporation of trehalose into the bacterial cell envelope is an antibiotic that is effective.
This disclosure relates to novel SARS-CoV-2 targeting sequences. Novel SARS-CoV-2 targeting oligonucleotides for the treatment of SARS-CoV-2 infection are also provided.
Aspects of the disclosure relate to compositions and methods for treating spinal muscular atrophy (SMA). The disclosure is based, in part, on isolated nucleic acids and vectors (e.g., viral vectors, such as rAAV vectors) encoding SMN1. In some embodiments, the expression of SMN1 is driven by a native SMN1 promoter or a variant thereof. In some embodiments, isolated nucleic acids and vectors of the disclosure have reduced toxicity and/or increased transgene expression relative to previously described SMN-encoding vectors.
C12Q 1/34 - Measuring or testing processes involving enzymes, nucleic acids or microorganismsCompositions thereforProcesses of preparing such compositions involving hydrolase
C12Q 1/6804 - Nucleic acid analysis using immunogens
87.
OLIGONUCLEOTIDES FOR TISSUE SPECIFIC GENE EXPRESSION MODULATION
This disclosure relates to a therapeutic combination of drugs for the treatment or management of a neurodegenerative disease, the combination comprising: a first conjugate comprising an RNA silencing agent and a first targeting agent that targets the first conjugate to the central nervous system, and a second conjugate comprising an antagonist of the RNA silencing agent and a second targeting agent that targets the second conjugate to a off-target tissue.
C12N 15/113 - Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides
A61K 47/54 - Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additivesTargeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
Methods for formation of graphene films, graphene films made thereby, and applications thereof. A method for the formation of a graphene film includes coating a polymeric graphene precursor on a substrate. The method includes irradiating the polymeric graphene precursor coated on the substrate with a pulsed high intensity light source emitting at more than a single wavelength and with a pulse duration of less than one second, to convert the polymeric graphene precursor to the graphene film.
An energy absorbing structure and method of making thereof is disclosed. The energy absorbing structure comprises an energy absorbing lattice structure having an irregular, but not random, lattice pattern. The irregular lattice pattern of the energy absorbing lattice structure may be a Voronoi cell pattern, which may be derived from a bovid skull horncore morphology. Other lattice patterns may be used, such as two-dimensional tessellations forming a distribution of asymmetric polygons or three-dimensional tessellations to form a distribution of asymmetric polyhedral shapes. The energy absorbing structure may further comprise one or more substrates to one or more sides of the energy absorbing lattice structure. The energy absorbing structure may be formed through additive manufacturing and has a variety of applications including, but not limited to, helmet liners, protective gear, shoe soles, packaging material, vehicle panels, or phone cases.
RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL (USA)
UNIVERSITY OF MASSACHUSETTS (USA)
Inventor
Bradbury, Allison, Marie
Sena-Esteves, Miguel
Abstract
Provided are gene therapy vectors, such as adeno-associated virus (AAV), designed for treatment of mutations in the neurofibromin 1 (NF1) gene. The disclosed gene therapy vectors provide a mini-NF1 cDNA to a subject in need which results in expression of a functional NF1 protein. Also provided are compositions, nanoparticles, extracellular vesicles, exosomes, or vector comprising the NF1 gene with nerve-cell specific and Schwann-cell specific promoters and methods of using the mini-NF1 gene with nerve-cell specific and Schwann-cell specific promoters in treating neurofibromatosis type 1. Also provided are novel mini-NF1 gene constructs.
The present disclosure relates to Neisseria meningitidis (Nme) 2 Cas9 (Nme2Cas9) and Nme2SmuCas9 variants comprising one or more amino acid substitutions with increased genome editing activities (e.g., improve nuclease and base editing efficiencies).
Provided herein, in various embodiments, are methods of treating a fragile X-associated disorder (e.g., fragile X syndrome), comprising administering to a subject in need thereof, a therapeutically effective amount of an agent that decreases expression of an aberrant fragile X messenger ribonucleoprotein 1 (FMR1) gene product (e.g., FMR1-217). Also provided herein, in various embodiments, are compositions (e.g., polynucleotides such as antisense oligonucleotides or pharmaceutical compositions) for decreasing expression of an aberrant FMR1 gene product.
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 diseasesGene therapy
A61P 25/28 - Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
C12N 15/11 - DNA or RNA fragmentsModified forms thereof
95.
RADIATION SOURCE AND BEAM LOCALIZATION USING MICROSTRUCTURED CONDUCTIVE ELEMENTS WITH SPATIOTEMPORAL DESIGN
Described here are systems and methods for determining the spatial location of a radiation source, such as a radiation source moving in a brachytherapy applicator (e.g., an afterloader catheter, a needle) during a brachytherapy procedure. Conductive elements coupled to the brachytherapy applicator are operable as radiation detectors that can measure spatiotemporal signal data to localize the position of the radiation source as it moves within the brachytherapy applicator. The conductive elements may include micro-structured wires (e.g., coaxial micro-structured wires), micro-structured conductive strips, conductive thin films, or other patterns of conductors. Other detector types may include ion chambers, solid-state detectors, or resistive electrodes.
The present invention is related to the field of gene editing. In particular, the gene editing is directed toward single nucleotide base editing. For example, such single nucleotide base editing results in a conversion of a mutated base pair to a wild type base pair. The high accuracy and precision of the presently disclosed single nucleotide base gene editor is accomplished by a fusion protein including an NmeCas9 nuclease and an inlaid nucleotide deaminase protein domain. The Nme2Cas9 protospacer interacting domain may be replaced with an SmuCas9 protospacer interacting domain.
Various embodiments disclosed relate to methods of manufacturing textured surfaces nanoimprint lithography with nanoparticulate inks. The present invention provides methods that allow flexible patterning of substrates with features having complex geometries.
G03F 7/00 - Photomechanical, e.g. photolithographic, production of textured or patterned surfaces, e.g. printed surfacesMaterials therefor, e.g. comprising photoresistsApparatus specially adapted therefor
B05D 1/00 - Processes for applying liquids or other fluent materials
C23C 16/04 - Coating on selected surface areas, e.g. using masks
C23C 16/455 - Chemical coating by decomposition of gaseous compounds, without leaving reaction products of surface material in the coating, i.e. chemical vapour deposition [CVD] processes characterised by the method of coating characterised by the method used for introducing gases into the reaction chamber or for modifying gas flows in the reaction chamber
98.
USE OF INVERTED TERMINAL REPEATS (ITRS) FROM ADENO-ASSOCIATED VIRUS SEROTYPES 8 AND RH.39 IN GENE THERAPY VECTORS
In some aspects, the disclosure provides recombinant AAV and nucleic acid constructs having novel inverted terminal repeats (ITRs), cap, and/or rep genes. In some aspects, the disclosure relates to gene transfer methods using rAAVs described herein.
H04L 41/12 - Discovery or management of network topologies
H04L 41/22 - Arrangements for maintenance, administration or management of data switching networks, e.g. of packet switching networks comprising specially adapted graphical user interfaces [GUI]
99.
ARTICLE COMPRISING NON-WELDABLE SUPERALLOYS AND METHODS OF MANUFACTURE THEREOF
An ink formulation for manufacturing a non-weldable superalloy, the ink formulation including: a superalloy particle, the superalloy particle including a primary element of Ni, Co, Fe, or a combination thereof, and a secondary element including an element of Group 4 to Group 14, or a combination thereof, of the Periodic Table of the Elements, other than the primary element, wherein the superalloy particle has a size of less than 30 micrometers; a binder including a polymer, and a solvent.
B22F 1/103 - Metallic powder containing lubricating or binding agentsMetallic powder containing organic material containing an organic binding agent comprising a mixture of, or obtained by reaction of, two or more components other than a solvent or a lubricating agent
B22F 1/05 - Metallic powder characterised by the size or surface area of the particles
B22F 1/107 - Metallic powder containing lubricating or binding agentsMetallic powder containing organic material containing organic material comprising solvents, e.g. for slip casting
B22F 3/20 - Manufacture of workpieces or articles from metallic powder characterised by the manner of compacting or sinteringApparatus specially adapted therefor by extruding
B22F 3/24 - After-treatment of workpieces or articles
B22F 9/08 - Making metallic powder or suspensions thereofApparatus or devices specially adapted therefor using physical processes starting from liquid material by casting, e.g. through sieves or in water, by atomising or spraying
The present disclosure relates to the field of rAAV delivery of transgenes. In some aspects, the disclosure relates to RNAi. Provided herein are recombinant adeno-associated virus (rAAV) vectors comprising modified ITRs. In some embodiments, the modified ITRs comprise a sequence encoding a shRNA, miRNA, or AmiRNA.
