Abstract: Methods and systems for synthesizing multicompartment capsules are disclosed, as well as multicompartment polymer capsules formed in accordance with disclosed techniques. At least one plurality of polymer capsules are formed via a capsule-forming process. A feed solution and a reservoir solution are provided, each comprising a biopolymer. The feed solution biopolymer and the reservoir solution biopolymer have opposite charges. Droplets of the feed solution are introduced into the reservoir solution, thereby forming via electrostatic complexation a plurality of polymer capsules. At least a portion of the resulting polymer capsules are then encapsulated in a larger polymer capsule via a similar process, wherein the feed solution utilized for the encapsulation process also comprises the formed smaller capsules.

Abstract: This invention relates to molecules, particularly polypeptides, more particularly fusion proteins that include a serpin polypeptide or an amino acid sequence that is derived from a serpin and second polypeptide comprising of at least one the following: an Fc polypeptide or an amino acid sequence that is derived from an Fc polypeptide; a cytokine targeting polypeptide or a sequence derived from a cytokine targeting polypeptide; a whey acidic protein (WAP) domain containing polypeptide or a sequence derived from a WAP containing polypeptide; and an albumin polypeptide or an amino acid sequence that is derived from a serum albumin polypeptide. This invention also relates to methods of using such molecules in a variety of therapeutic and diagnostic indications, as well as methods of producing such molecules.

Abstract: The present application provides immune cells (such as T cells) comprising a chimeric antibody-T cell receptor (TCR) construct (caTCR) and a chimeric signaling receptor (CSR) construct. The caTCR comprises an antigen-binding module that specifically binds to a target antigen and a T cell receptor module (TCRM) capable of recruiting at least one TCR-associated signaling molecule, and the CSR comprises a ligand-binding domain that specifically binds to a target ligand and a co-stimulatory signaling domain capable of providing a stimulatory signal to the immune cell. Also provided are methods of making and using these cells.

Abstract: Genome editing systems, guide RNAs, dead guide RNAs, and CRISPR-mediated methods are provided for altering portions of a target nucleic acid.

Abstract: Herein is reported a method for the co-cultivation of single deposited B-cells, which can be of any source, with EL-4 B5 feeder cells in a suitable co-cultivation medium. In the herein reported methods the EL-4 B5 cells have been irradiated with a dose of less than 40 Gy, preferably 9.5 Gy or less. Thereby the EL-4 B5 cells have a higher viability and maintain the ability to divide in cultivation at doses less than 6 Gy.

Abstract: The present disclosure relates to particular subsets of CD4+ and CD8+ T-cells, methods of isolating and generating these cells, compositions comprising these cells, and methods of treatment of a tumor or cancer by administering these cells alone or in combination with each other and/or additional therapies.

Abstract: The present invention relates to a medium composition for reinforcing the efficacy of stem cells, including ethionamide, a method of reinforcing the efficacy of stem cells, including culturing stem cells in the medium composition, a method of preparing stem cells with reinforced efficacy, stem cells prepared by the above-mentioned method, and a use thereof. According to the present invention, the anti-inflammatory effect of mesenchymal stem cells and expression levels of paracrine factors may be effectively improved by a simple method of treating mesenchymal stem cells with ethionamide, and the stem cells obtained by the above method may be effectively used for preventing or treating an inflammatory disease or a degenerative brain disease.

Abstract: The present invention pertains to antigen recognizing constructs against COL6A3 antigens. The invention in particular provides novel T cell receptor (TCR) based molecules which are selective and specific for the tumor expressed antigen COL6A3. The TCR of the invention, and COL6A3 antigen binding fragments derived therefrom, are of use for the diagnosis, treatment and prevention of COL6A3 expressing cancerous diseases. Further provided are nucleic acids encoding the antigen recognizing constructs of the invention, vectors comprising these nucleic acids, recombinant cells expressing the antigen recognizing constructs and pharmaceutical compositions comprising the compounds of the invention.

Abstract: Systems and methods for rapid gene set enrichment analysis and applications thereof are described. These systems and methods enable improved prioritization of relevant gene sets while maintaining a relatively lower false positive rate. Additionally, the ability to accelerate enrichment analysis and analyze hundreds of thousands of gene sets is described.

Abstract: Provided is a plant or plant part comprising a polynucleotide encoding a mutant TriA polypeptide, the expression of the polynucleotide confers to the plant or plant part tolerance to herbicides.

Abstract: An apparatus for collecting or culturing cells or cell colonies includes: a common substrate formed from a flexible resilient polymeric material and having a plurality of wells formed therein; and a plurality of rigid cell carriers releasably connected to said common substrate, with said carriers arranged in the form of an array, and with each of the carriers resiliently received in one of the wells. A method of collecting or culturing cells or cell colonies with such an apparatus is carried out by depositing a liquid media carrying cells on the apparatus so that said cells settle on or adhere to said the carriers; and then (c) releasing at least one selected carrier having said cells thereon by gradual application of release energy to each carrier from the cavity in which it is received (e.g., by pushing with a probe).

Abstract: According to the present disclosure, a technology for efficiently introducing a desired foreign substance from the outside of eukaryotic cells into at least the cytoplasm (and the nucleolus) of the cells is provided. A method disclosed here includes a step of preparing a construct for introducing a foreign substance including a carrier peptide fragment composed of any of amino acid sequences: KKRTLRKKKRKKR (SEQ ID NO: 1), KKRTLRKRRRKKR (SEQ ID NO: 2), KKRTLRKRKRKKR (SEQ ID NO: 3) and KKRTLRKKRRKKR (SEQ ID NO: 4), and a foreign substance that is bound to an N-terminal side and/or C-terminal side of the carrier peptide fragment, a step of supplying the construct for introducing a foreign substance to a sample containing desired eukaryotic cells, and a step of incubating the sample to which the construct for introducing a foreign substance is supplied and introducing the construct into eukaryotic cells in the sample.

Abstract: Disclosed herein are compositions for linking DNA binding domains and cleavage domains (or cleavage half-domains) to form non-naturally occurring nucleases with alternative configurations. Also described are methods of making and using compositions comprising these linkers.

Abstract: A device may receive images of a patient, and may perform segmentation of surfaces on the images to create a 3D model. The device may identify normal tissue regions and atrial fibrosis (AF) regions in the 3D model, and may divide the 3D model into the normal tissue regions and the AF regions. The device may assign first cell and tissue properties to the normal tissue regions, and may assign second cell and tissue properties to the AF regions. The device may perform simulations on the normal tissue regions and the AD regions, based on the first and second cell and tissue properties, to generate simulation results, and may extract first features from the simulation results. The device may extract second features from the images, and may process the first and second features, with a model, to select a feature that is predictive of atrial fibrillation recurrence.

Abstract: The present invention provides compositions and methods for regulating the specificity and activity of T cells. In one embodiment, the invention provides a type of chimeric antigen receptor (CAR) wherein the CAR is termed a “KIR-CAR” which is a CAR design comprising a component of a receptor naturally found on natural killer (NK) cells. In one embodiment, the NK receptor includes but is not limited to a naturally occurring activating and inhibitory receptor of NK cells known as a killer cell immunoglobulin-like receptor (KIR).

Abstract: The present invention relates to a medium composition for improving stem cell migration, which includes ethionamide, and a use thereof. According to the present invention, the migration of stem cells may be effectively improved by the adjustment of a culture environment, which is a simple and safe method, without using gene manipulation or a viral vector, and the stem cells improved in migration by the method may be effectively used as a stem cell therapeutic agent that is able to function by rapidly migrating to the damaged region after transplantation.

Abstract: The present invention relates to artificial transcription factors (ATFs) that alter gene expression, including inducing pluripotency in cells or promoting the conversion of cells to specific cell fates. In particular, provided herein is a zinc-finger based ATF library that can be screened in cells by looking for expression of a specific gene (e.g., reporter expression), monitoring for cell surface markers or morphology, or via functional assays.

Abstract: The present invention relates to adenovirus E4ORF1 gene and to endothelial cells engineered to express the E4ORF1 gene. The present invention also relates to uses of the E4ORF1 gene, and cells expressing the E4ORF1 gene, and to compositions comprising the E4ORF1 gene, or comprising cells expressing the E4ORF1 gene.

Abstract: A bioreactor includes a scaffold, a scaffold support, and a manifold. The scaffold is seeded with a plurality of cells. The scaffold has an extended state and a non-extended state. The scaffold support that selectively modifies a state of the scaffold from the non-extended state to the extended state. A manifold is configured to provide a medium to the scaffold. The state of the scaffold from the non-extended state to the extended state is modified at a rate tuned to maintain a cell density associated with the plurality of cells within a particular density range.

Abstract: Non-human animals, and methods and compositions for making and using the same, are provided, wherein said non-human animals comprise a humanization of an endogenous cluster of differentiation (CD) gene, in particular a humanization of a CD47 gene. Said non-human animals may be described, in some embodiments, as having a genetic modification to an endogenous CD47 gene so that said non-human animals express a CD47 polypeptide that includes a human portion and a non-human portion (e.g., a murine portion).

Abstract: The present invention relates to a method for isolating extracellular vesicles using cations, and more particularly, to a method for isolating extracellular vesicles from various samples by using the affinity between the extracellular vesicles and cations. A method for isolating extracellular vesicles according to the present invention does not require expensive equipment, can be applied irrespective of sample amount, and has the advantage of being capable of efficiently isolating the extracellular vesicles while preserving the shape or characteristics thereof. Moreover, the method according to the present invention can be combined with existing isolation methods to maximize extracellular vesicle isolation efficiency, and can be applied to disease diagnosis, disease treatment, and multi-omics research using isolated extracellular vesicles, as well as to research on the properties of extracellular vesicles.

Abstract: The present invention provides novel methods and systems, including cell lines, recombinant polynucleotide constructs, compositions, and kits, for targeted yet universal genomic manipulation.

Abstract: Chimeric antigen receptors containing tumor necrosis factor receptor superfamily member transmembrane domains are disclosed. Nucleic acids, recombinant expression vectors, host cells, antigen binding fragments, and pharmaceutical compositions, relating to the chimeric antigen receptors are also disclosed. Methods of treating or preventing cancer in a subject, and methods of making chimeric antigen receptor T cells are also disclosed.

Abstract: Provided is a genetically modified non-human animal, in which at least one copy of the endogenous nucleotide sequence encoding Protein C in the genome of said the non-human animal has been replaced by a nucleotide sequence encoding human Protein C or a functional fragment or variant thereof. Also provided are vectors, cells, and methods for the production of such non-human animals. Further provided are methods of testing agents for their ability to alter to the level and/or functional activity of human protein C, for example, to test their potential therapeutic efficacy.

Abstract: A microfluidic device system includes a channel having an entrance and an exit, a height at the entrance being greater than a height at the exit. The height of the channel may decrease continuously from the height at the entrance to the height at the exit. Cells or particles or beads traveling through the channel become trapped based on their size and/or deformability. A visual sensor captures images of the trapped cells or particles or beads, and image software analyzes the captured images to provide size and/or deformability and/or fluorescence information. A method of fabricating such a microfluidic device includes introducing a glass wafer to an etching solution at a specific rate such that a first end of the glass wafer is etched longer than other portions of the glass wafer.

Abstract: The present invention relates to a variant of BPIFB4 protein (Bactericidal/Permeability Increasing protein family B, member 4) and to a polynucleotide or a vector encoding said variant of BPIFB4 protein and to their use for the treatment of pathologies involving impairment of nitric oxide signalling.

Abstract: The present invention provides an immune effector cell that comprises a chimeric antigen receptor (CAR) specific for a tag of a tagged polypeptide, wherein said polypeptide binds to an antigen of a target cell, and a chimeric costimulatory receptor (CCR) specific for a further antigen. The CCR is not able to mediate said immune response on its own but boosts the immune response of said immune effector cell triggered by the CAR.

Abstract: Methods and systems for generating MGE precursor cells in vitro as well as compositions of enriched MGE precursor cells are provided. The methods and systems provide efficient production of MGE precursors. The methods and systems disclosed herein provide functional MGE precursors which differentiate into functional GABAergic interneurons.

Abstract: This disclosure relates to the field of molecular biology. Provided are novel genes that encode pesticidal proteins. These pesticidal proteins and the nucleic acid sequences that encode them are useful in preparing pesticidal formulations and in the production of transgenic pest-resistant plants. Methods to create or alter pesticidal proteins are provided for altered or enhanced pesticidal activity.

Abstract: The present invention provides lipid aggregate compositions having at least two cationic lipids in combination with one or optionally more than one non-cationic lipids for the in vitro and/or in vivo delivery of biologically active molecules including nucleic acids, specifically DNA and RNA, and proteins into cells and tissues. Methods are also provided that use the compounds of the present invention to deliver biologically active molecules, into cells and tissues to facilitate the expression of target proteins therein. In some non-limiting embodiments, the subject lipid aggregate compositions can be used to deliver nucleic acid molecules to facilitate the expression of proteins involved in cellular reprogramming and genome editing applications.

Abstract: Disclosed herein are genome editing systems and related methods which allow for the detection and quantitative measurement of all possible on-target gene editing outcomes, including targeted integration. The compositions and methods described herein rely on the use of donor templates comprising a 5? homology arm, a cargo, a one or more priming sites, a 3? homology arm, and optionally stuffer sequence.

Abstract: Disclosed herein are recombinant meganucleases engineered to recognize and cleave a recognition sequence present in the human mitochondrial DNA (mtDNA). The disclosure further relates to the use of such recombinant meganucleases in methods for producing genetically-modified eukaryotic cells, and to a population of genetically-modified eukaryotic cells wherein the mtDNA has been having modified or edited.

Abstract: Biocompatible, mechanically-dynamic thermoresponsive devices, methods for forming the devices, and exemplary applications for the devices are described. The devices include a series of wells therein and provide for temperature-controlled mechanostimulation of single cells or groups of cells that can be retained in the wells of a device. Mechanostimulation can be single instance of any duration, continuous, or regular or irregular cyclic mechanostimulation of single cells, cell clusters, cell spheroids, or organoids and may be utilized in any of a variety of biomedical applications including, without limitation, cellular engineering, cellular phenotyping, and drug discovery/screening.

Abstract: The present disclosure belongs to the field of biopharmaceuticals, and in particular, relates to a multi-domain active protein for treating metabolic diseases. The multi-domain active protein has a structural formula as shown in Formula I: A-La-F-Lb-B. The multi-domain active protein of the present disclosure has a long half-life and supports a once-a-week administration frequency. The GLP-1R agonist activity of the multi-domain active protein is increased up to over 200 times. The multi-domain active protein has good stability in vitro and in vivo, and shows low immunogenicity potential. As introduction of non-natural amino acids is not required and chemical synthesis and crosslinking steps are not involved, the multi-domain active protein can be prepared recombinantly. Therefore, the preparation process is greatly simplified.

Abstract: Provided herein are, inter alia, nucleic acid conjugates including a non-cell penetrating ribonucleic acid compound attached at its 3? end to a phosphorothioate polymer. Attachment of the phosphorothioate polymer to the non-cell penetrating ribonucleic acid conveys stability to and allows for efficient intracellular delivery of the non-cell penetrating ribonucleic acid. The nucleic acid conjugates provided herein including embodiments thereof are useful, inter alia, for the treatment of cancer, inflammatory disease, and pain.

Abstract: Provided herein are reporter T-cells containing a reporter operably linked to the Nur77 locus. Also provided are methods for screening for an activity of a recombinant receptor, including those containing an extracellular antigen-binding domain and an intracellular signaling domain, such as a chimeric antigen receptor (CAR), including assessing activity of a cell expressing the recombinant receptor based on a detectable expression of a reporter molecule responsive to a signal through the intracellular signaling region of the recombinant receptor. In some embodiments, the activity assessed is an antigen-dependent or an antigen-independent activity. In some embodiments, the methods can be used to screen a plurality of reporter cells each containing a nucleic acid molecule encoding a candidate recombinant receptor, e.g. CAR, and assessing such cells for one or more property or activity. The methods can be high-throughput.

Abstract: Disclosed herein are methods and compositions for generation of cell lines to promote unnatural amino acid-containing protein production using genome engineering technology.

Abstract: A system and method are provided for harvesting target biological substances. The system includes a substrate and a first and second channel formed in the substrate. The channels longitudinally extending substantially parallel to each other. A series of gaps extend from the first channel to the second channel to create a fluid communication path passing between a series of columns with the columns being longitudinally separated by a predetermined separation distance. The system also includes a first source configured to selectively introduce into the first channel a first biological composition at a first channel flow rate and a second source configured to selectively introduce into the second channel a second biological composition at a second channel flow rate. The sources are configured to create a differential between the first and second channel flow rates to generate physiological shear rates along the second channel that are bounded within a predetermined range.

Abstract: One disadvantage of adeno-associated virus (AAV) is low gene expression efficiency due to delayed expression of the inserted gene. Provided is a vector plasmid for producing a vector genome to be inserted into an adeno-associated virus (AAV). The vector plasmid is provided with a vector genome cassette as a template of the vector genome, and the vector genome cassette is provided with: (1) an expression cassette including a nucleic acid molecule encoding a target gene and (b) a nucleic acid molecule encoding an expression regulatory region that allows expression of the target gene; and (2) two nucleic acid molecules positioned on both sides of the expression cassette and encoding inverted terminal repeats (ITRs). Also provided is a pharmaceutical composition containing the AVV vector, for treating or preventing an eye disease or disease associated with same.

Abstract: The invention relates to the field of tissue engineering and regenerative medicine, and particularly to a three-dimensional biomimetic tissue scaffold that exploits the use of three-dimensional print technology. Surface energy is controlled by precisely placing polymers with differing surface chemistry, and using surface texture and bulk composition to pattern absorbable and non-absorbable polymers for the purpose of promoting functional healing in a mammalian body.

Abstract: The invention discloses an immunoglobulin-binding magnetic bead, comprising a porous matrix and one or more magnetic particles embedded in said matrix, wherein said matrix comprises a porous polymer and at least 10 mg/ml Fc-binding proteinaceous ligands covalently coupled to said porous polymer.

Abstract: Some embodiments of the invention include a nucleic acid molecule comprising natural nucleotides, non-natural nucleotides, an LNA which comprises one or more RNA core molecules, or an RNA molecule which comprises more than one RNA core molecule. Some embodiments of the invention include a nucleic acid molecule comprising an RNA molecule which comprises more than one RNA core molecule. Other embodiments of the invention include a nucleic acid molecule comprising a DNA molecule encoding the RNA molecule (e.g., vector or viral vector). Other embodiments include compositions or pharmaceutical compositions that comprise the nucleic acid molecule. Some embodiments of the invention comprise reducing miR-143 in a cell. Other embodiments of the invention include methods to deliver a protein across the BBB. Other embodiments include methods for treating disease (e.g., LSD, neuronopathic disease, neurodegenerative disease, Hurler syndrome, or MPS I). Additional embodiments of the invention are also discussed herein.

Abstract: The present invention relates antidotes to anticoagulants targeting factor Xa. The antidotes are factor Xa protein derivatives that bind to the factor Xa inhibitors thereby substantially neutralizing them but do not assemble into the prothrombinase complex. The derivatives describe herein lack or have reduced intrinsic coagulant activity. Disclosed herein are methods of stopping or preventing bleeding in a patient that is currently undergoing anticoagulant therapy with a factor Xa inhibitor.

Abstract: The present invention relates to microfluidic fluidic devices, methods and systems as microfluidic kidney on-chips, e.g. human Proximal Tubule-Kidney-Chip, Glomerulus (Kidney)-Chip, Collecting Duct (Kidney)-Chip. Devices, methods and systems are described for drug testing including drug transport and renal clearance. Further, such devices, methods and systems are used for determining drug-drug interactions and their effect upon renal transporter functions. Importantly, they may be used for pre-clinical and clinical drug development for treating kidney diseases and for personalized medicine.

Abstract: An observation vessel includes a holding portion configured to hold an observation object and an accommodation portion at least partially formed of a transparent curved surface and configured to position the holding portion. The holding portion is configured to hold the observation object at a set position separated from the curved surface toward a center of curvature of the curved surface in a first state of being positioned at a first position by the accommodation portion.

Abstract: The present invention relates to a pharmaceutical composition for preventing or treating neonatal hypoxic ischemic encephalopathy (HIE), comprising thrombin-treated stem cells or exosomes derived therefrom as an active ingredient, and a method for producing the same. According to the present invention, the thrombin-treated stem cell or the exosome derived therefrom has an increased expression of growth factors, immunoregulatory factors, antioxidation factors, or regeneration factors compared to a group not treated with thrombin and also enhances a neuronal apoptosis inhibitory effect, and thus has an advantage in that the therapeutic effect thereof on neonatal hypoxic ischemic encephalopathy (HIE) is excellent.

Abstract: A method of generating a cellular model of Alzheimer's disease (AD) comprises integrating AD related gene to hiPSC to induce increased beta secretase and/or Abeta 42 peptides, and the cellular model of Alzheimer's disease (AD) is prepared by the method.

Abstract: The disclosure provides methods for generating an optimized nucleotide sequence encoding an engineered influenza structural protein and the optimized nucleotide sequences obtained therefrom. The optimized nucleotide sequences can be used in a reverse genetics system to facilitate the rescue of infectious influenza virus containing the engineered structural proteins and/or enhance viral titers. Also provided are methods of preparing an influenza vaccine composition using the optimized nucleotide sequences, as well as methods of inducing an immune response using the influenza vaccine composition.

Abstract: The invention provides an isolated and purified nucleic acid sequence encoding a chimeric antigen receptor (CAR) directed against B-cell Maturation Antigen (BCMA). The invention also provides host cells, such as T-cells or natural killer (NK) cells, expressing the CAR and methods for destroying multiple myeloma cells.

Abstract: In this application, the provided are: a Down syndrome rat model characterized in that a rat gene homologous to at least one gene present on a human chromosome 21 or fragment thereof is a trisomy and is transmittable to progeny; or a Down syndrome rat model characterized in that it comprises a human chromosome 21 or fragment thereof, or an exogenous rat chromosome or fragment thereof on which a rat gene homologous to the human chromosome 21 or fragment thereof is present, wherein at least one gene on the human chromosome 21 or fragment thereof or on the exogenous rat chromosome or fragment thereof is added to endogenous rat genes homologous to the at least gene so as to become a trisomy and to be transmittable to progeny: and a method for producing the Down syndrome rat model.