Abstract: Non-human animal genomes, non-human animal cells, and non-human animals comprising a humanized PNPLA3 locus and methods of making and using such non-human animal genomes, non-human animal cells, and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized PNPLA3 locus express a human PNPLA3 protein or a chimeric PNPLA3 protein, fragments of which are from human PNPLA3. Methods are provided for using such non-human animals comprising a humanized PNPLA3 locus to assess in vivo efficacy of human-PNPLA3-targeting reagents such as nuclease agents designed to target human PNPLA3.

Abstract: Provided are methods and compositions for obtaining functionally enhanced derivative effector cells obtained from directed differentiation of genomically engineered iPSCs. The derivative cells provided herein have stable and functional genome editing that delivers improved or enhanced therapeutic effects. Also provided are therapeutic compositions and the used thereof comprising the functionally enhanced derivative effector cells alone, or with antibodies or checkpoint inhibitors in combination therapies.

Abstract: Recombinant poly-IgA oligomers that form high-order oligomers resembling poly-IgA of IgA nephropathy are provided. Injection of recombinant IgA oligomers in an animal model produces prominent renal glomerular mesangial deposition of recombinant poly IgA oligomer, as in IgA nephropathy patients. Thus, producing a model of IgAN pathology that is able to provide screening and evaluation of therapeutic drugs and diagnostic tests.

Abstract: The present invention relates to methods for targeted insertion of at least one nucleic acid sequence/s of interest into a target genomic locus of a mammalian cell. More specifically, the methods of the invention are based on using nucleic acid cassettes comprising the nucleic acid sequence/s of interest and at least one recognition signal sequence (RSS), for insertion of the nucleic acid sequence of interest into the target genomic locus that is mediated by RAG-catalyzed recombination. The invention further provides cassettes, vectors and vehicles and cells comprising said cassettes, compositions and uses thereof in immunotherapy.

Abstract: Chimeric antigen receptors containing mesothelin antigen binding 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: The invention provides a chimeric antigen receptor (CAR) comprising an antigen binding domain comprising SEQ ID NOs: 1-6, a transmembrane domain, and an intracellular T cell signaling domain. Nucleic acids, recombinant expression vectors, host cells, populations of cells, antibodies, or antigen binding portions thereof, and pharmaceutical compositions relating to the CARs are disclosed. Methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal are also disclosed.

Abstract: Disclosed are methods and compositions for in situ germline genome engineering. The disclosed methods and compositions may be utilized for germline genome engineering in a subject having a reproductive organ containing a fertilized zygote, via: (i) isolating or obtaining the reproductive organ from the subject after a time period following insemination of the subject; (ii) introducing a reagent composition into the reproductive organ, the reagent composition comprising a nuclease system and/or an exogeneous polynucleotide; and (iii) electroporating the reproductive organ.

Abstract: Provided herein are nucleic acids for expressing modified ligand-gated ion channel proteins in excitable cells or secretory cells, such as nerves and neurons and optionally including viral sequences, such as Adeno-associated virus sequences, for delivery to excitable cells or secretory cells of a patient. Also provided herein are methods of modulating cell membrane potentials in an excitable cell or secretory cell, and for treatment of a disease or disorder associated with the nervous system in a patient, such as chronic pain or itch.

Abstract: Viral vectors are provided for use as genetic immunotherapeutic agents, including preventive and therapeutic vaccines as well as compositions to enhance cellular immune responses and innate immune responses. The vectors are particularly useful for treating or preventing cancer and infectious diseases. The vectors include lentiviral vectors that encode one or more antigens, a combination of adjuvants, and optionally may encode one or more soluble and secreted checkpoint inhibitor molecules. The adjuvants include latent membrane protein 1 (LMP1) from Epstein Barr virus and a fusion protein including LMP1 with in which the intracytoplasmic domain has been replaced by human IPS1 or a variant thereof capable of activating the STING pathway. The vector-encoded sequences are codon optimized for human expression.

Abstract: A method of inhibiting an overactive fibroblast growth factor receptor 3 (FGFR3) in a cell by contacting the cell with a composition that contains an effective amount of Pheophorbide a, Pyropheophorbide a, or an active derivative thereof. Also disclosed is a method for treating a disorder associated with an overactive FGFR3 with a composition containing an effective amount of Pheophorbide a, Pyropheophorbide a, or an active derivative thereof. Further, a composition for treating a disorder associated with an overactive FGFR3 is described. The composition contains an ethanol extract of Amaranthus viridis.

Abstract: The present invention provides a recombinant adipose-derived stem cell and a recombinant method thereof, and belongs to the technical field of genetic engineering, where an adenovirus carrying an hFIX gene is transfected into an adipose-derived stem cell to obtain the recombinant adipose-derived stem cell. In the present invention, an adenovirus carrying an hFIX gene is transfected into an adipose-derived stem cell, and the recombinant adipose-derived stem cell obtained after the transfection can express an hFIX protein.

Abstract: Disclosed are bioprinted, three-dimensional, biological skin tissues comprising: a dermal layer comprising dermal fibroblasts; and an epidermal layer comprising keratinocytes, the epidermal layer in contact with the dermal layer to form the three-dimensional, engineered, biological skin tissue. Also disclosed are arrays of engineered skin tissues and methods of making engineered skin tissues.

Abstract: An object of the present invention is to provide a novel method which enables convenient preparation of cells exhibiting functions close to that of intestinal epithelial cells of living bodies, and use of the method. The differentiation of induced pluripotent stem cells into intestinal epithelial cells is induced by step of differentiating induced pluripotent stem cells into endoderm-like cells; step of differentiating the endoderm-like cells obtained in step into intestinal stem cell-like cells; and step of differentiating the intestinal stem cell-like cells obtained in step into intestinal epithelial cell-like cells, wherein step includes culture in the presence of a MEK1 inhibitor, a DNA methyltransferase inhibitor, a TGF-? receptor inhibitor, and EGF and under the condition that cAMP is supplied to the cells.

Abstract: The present invention provides a non-human animal having human interleukin-34 (IL-34) in the body thereof; a method for producing a non-human animal having human microglia, which includes transplanting human CD34-positive hematopoietic stem cells into the non-human animal having human IL-34 in the body; and a method for producing human microglia, which includes obtaining human microglia from the non-human animal having human microglia.

Abstract: Provided herein are compositions and methods for modulation of immune response via PYRIN domain-only proteins POP1 and/or POP3. In particular, POP1 and/or POP3 are inhibited to enhance an immune response (e.g., to treat or prevent infection), or POP1 and/or POP3 are administered or activated to reduce an immune response (e.g., to treat or prevent autoimmune or inflammatory disease).

Abstract: This invention relates to the efficient generation of cholangiocyte progenitor (CP) cells. Foregut stem cells (FSCs) are cultured in a hepatic induction medium comprising bone morphogenetic protein (BMP) and a TGF? signalling inhibitor to produce a population of hepatoblasts. The hepatoblasts are then cultured in a biliary induction medium comprising fibroblast growth factor (FGF), retinoic acid and a TGF? ligand to produce a population of cholangiocyte progenitors (CPs). The cholangiocyte progenitors (CPs) may be matured into cholangiocyte-like cells (CLCs) that display functional properties of Common Bile Duct (CBD) cholangiocytes. Methods, kits, cell populations and uses of these cell populations are provided.

Abstract: The present invention relates to Chimeric Antigen Receptors (CAR) that are recombinant chimeric proteins able to redirect immune cell specificity and reactivity toward selected membrane antigens, and more particularly in which extracellular ligand binding is a scFV derived from a CD123 monoclonal antibody, conferring specific immunity against CD123 positive cells. The engineered immune cells endowed with such CARs are particularly suited for treating lymphomas and leukemia.

Abstract: A method for creating an animal model of traumatic optic nerve injury, including fully exposing an internal segment of an optic canal as well as adjacent anterior skull base, posterior ethmoid sinus and lateral sphenoid sinus walls through an ethmoid sinus-sphenoid sinus operation pathway under an endoscope, and impacting different sites of the internal segment of the optic canal with controllable impact force to cause optic nerve injury so as to prepare a controllable and quantifiable TONI bionic elastic injury animal model reflecting contusion to an internal segment of an optic canal in a human TONI clinical injury state. With less intracranial combined injury to the animal, the survival rate is high. Different sites of the optic canal are impacted with quantifiable elastic force for the quantitative and qualitative purposes with respect to the injured parts and the injury degree.

Abstract: Provided are vesicles derived from bacteria belonging to the genus Micrococcus, a composition and a use thereof, wherein the vesicles and the composition comprising the same may be effectively used for the development of a method of diagnosing gastric cancer, pancreatic cancer, cholangiocarcinoma, breast cancer, ovarian cancer, bladder cancer, myocardial infarction, cardiomyopathy, atrial fibrillation, variant angina, chronic obstructive pulmonary disease (COPD), dementia, or diabetes.

Abstract: This invention relates to soluble forms of F glycoprotein from Hendra and Nipah virus and to compositions comprising soluble forms of F glycoprotein from Hendra and Nipah virus. This invention further relates to soluble oligomers of F glycoprotein from Hendra and Nipah virus. This invention also relates to nucleic acids encoding soluble forms of F glycoprotein from Hendra and Nipah virus. This invention also relates to diagnostic and therapeutic methods using the soluble forms of F glycoprotein from Hendra and Nipah virus. Further, this invention relates to antibodies, including neutralizing antibodies, and to vaccines for the prevention, diagnosis and treatment of infection by Hendra and Nipah viruses.

Abstract: This invention relates generally to methods and compositions for diagnosing and treating disorders associated with elevated levels of Toll-like Receptor 4 (TLR4) ligands and other biomarkers. The invention also relates to methods of treating, delaying the progression of, or otherwise ameliorating a symptom of a disorder associated with elevated levels of TLR4 ligands and other biomarkers using agents that interfere with or otherwise antagonize TLR4 signaling, including neutralizing anti-TLR4 antibodies.

Abstract: Disclosed are compositions and methods for treatment of atherosclerosis and atherosclerotic plaques. In some forms, the compositions and methods can prevent, inhibit, or reduce atherosclerosis. In some forms, the compositions and methods can prevent, inhibit, or reduce atherosclerotic plaques. In particular, compositions comprising a plaque-homing element, a CendR-activating element, and a plaque-inhibiting element are disclosed.

Abstract: The present invention provides a novel use of fibroblast growth factor 2 (FGF-2), i.e., a use of FGF-2 in preparation of medicine. The uses of the medicine are the following (a) and/or (b) and/or (c): (a) the prevention and/or treatment of lung injury; (b) the prevention and/or treatment of influenza; (c) the prevention and/or treatment of diseases caused by influenza viruses.

Abstract: Genetically modified non-human animals expressing human EPO from the animal genome are provided. Also provided are methods for making non-human animals expressing human EPO from the non-human animal genome, and methods for using non-human animals expressing human EPO from the non-human animal genome. These animals and methods find many uses in the art, including, for example, in modeling human erythropoiesis and erythrocyte function; in modeling human pathogen infection of erythrocytes; in in vivo screens for agents that modulate erythropoiesis and/or erythrocyte function, e.g. in a healthy or a diseased state; in in vivo screens for agents that are toxic to erythrocytes or erythrocyte progenitors; in in vivo screens for agents that prevent against, mitigate, or reverse the toxic effects of toxic agents on erythrocytes or erythrocyte progenitors; in in vivo screens of erythrocytes or erythrocyte progenitors from an individual to predict the responsiveness of an individual to a disease therapy.

Abstract: Provided are a knockout mouse, a method for screening a substance for suppressing mesial temporal lobe epilepsy, and a method for selecting a technique for suppressing mesial temporal lobe epilepsy. A knockout mouse 30 or more days of age that has lost the function of the Girdin gene in at least the nervous tissues and exhibits the phenotypes of (1), (2), and (3) below. (1) hippocampal sclerosis should be present, (2) extrahippocampal brain damage should be limited, and (3) spontaneous epilepsy that can be said to be of hippocampal origin should be present.

Abstract: A method of obtaining a cardiac multipotent or unipotent cell, comprising: i) providing a cell of a first type which is not a cardiac multipotent or unipotent cell; ii) introducing into the cell of a first type an agent capable of remodeling the chromatin and/or DNA of the cell, wherein the agent capable of remodeling the chromatin and/or DNA is a histone acetylator, an inhibitor of histone deacetylation, a DNA demethylator, and/or a chemical inhibitor of DNA methylation; iii) introducing into the cell of a first type a reprogramming polypeptide and/or a polynucleotide encoding said reprogramming polypeptide, wherein the reprogramming polypeptide comprises Mesp1, Brachyury (T), Nkx2.5, and/or Tbx5; and iv) placing or maintaining the cell in a cardiac cell culture medium and maintaining intracellular levels of the reprogramming polypeptide or the polynucleotide encoding the reprogramming polypeptide for a sufficient period of time to allow a cardiac multipotent or unipotent cell to be obtained.

Abstract: The present invention provides transgenic, large non-human animal models of Duchenne muscular dystrophy, Becker muscular dystrophy, and DMD-associated dilated cardiomyopathy, as well as methods of using such animal models in the identification and characterization of therapies for Duchenne muscular dystrophy, Becker muscular dystrophy, and DMD-associated dilated cardiomyopathy.

Abstract: Compounds effective in inhibiting replication of Hepatitis C virus (“HCV”) are described. This invention also relates to processes of making such compounds, compositions comprising such compounds, and methods of using such compounds to treat HCV infection.

Abstract: The present invention provides antibodies that bind to prokineticin receptors (PROKRs) and methods of using same. According to certain embodiments of the invention, the antibodies are fully human antibodies that bind to human PROKR1 and/or PROKR2. The present invention includes antibodies that bind cell surface-expressed PROKR1 and/or PROKR2. In certain embodiments, the antibodies of the present invention are capable of blocking prokineticin (PK)-mediated activation of one or more PROKR. The antibodies of the invention are useful for the treatment of various diseases and disorders mediated by prokineticin signaling.

Abstract: The present invention relates to a transgenic animal model system based on the development of transgenic mice bearing components of the human immune system. Specifically, the invention relates to a Flk2 deficient Rag?/??c?/? transgenic mouse and the engraftment of said mouse with human hematopoietic stem cells. The present invention further provides methods for increasing the numbers of functionally competent human dendritic cells and the hematopoietic targets cells that they interact with in said transgenic mouse through the administration of Flk2L. The transgenic animal model system of the invention may be used for testing human vaccine candidates, for screening potential immune adjuvants and for developing novel therapeutics.

Abstract: Compositions and methods for identifying new treatments for Facioscapulohumeral muscular dystrophy (FSHD), and uses thereof.

Abstract: The present disclosure relates to an ASD genetically engineered model carrying a deletion of Shank2 gene and having reduced NMDA receptor function. According to the present disclosure, genetically engineered mice that show the clinical features of ASD due to the deletion of the Shank2 gene can be obtained, and the genetically engineered mice can be effectively used to screen candidate therapeutic agents.

Abstract: The present invention relates to a method of developing a Tumor Model System. The invention deals with a tumor model system with adhesion deprived cells. This observation provides a new method for primary detection of transformation of adhesion-deprived cells and tumorigenicity. The adhesion-deprived cells are capable of metastasizing at distant sites and the model system includes both the tumor formation and metastasis.

Abstract: The present invention relates to a mutant human alpha-synuclein with increased toxicity compared to wild-type alpha-synuclein, or a homologue thereof, wherein the mutant alpha-synuclein or homologue thereof comprises at least one amino acid substitution selected from the group consisting of a substitution at the alanine at position 56 (A56), at the alanine at position 76 (A76), at the methionine at position 127 (M127) and/or at the valine at position 118 (V118), as defined in the claims. Further, the invention relates to a polynucleotide encoding the mutant alpha-synuclein or homologue thereof, or an expression vector comprising said polynucleotide, a cell comprising the polynucleotide or expression vector, as defined in the claims. Also, a non-human animal comprising the cell of the invention is provided, as defined in the claims. Finally, the invention provides methods for identifying a substance that prevents or reduces toxicity of alpha-synuclein, as defined in the claims.

Abstract: The present invention relates to a technique for inducing epilepsy and a non-human animal model of epilepsy. More particularly, the present invention relates to a method for inducing epilepsy in an animal, a non-human animal model of epilepsy, and a method for manufacturing the same.

Abstract: Non-human animals, cells, methods and compositions for making and using the same are provided, wherein the non-human animals and cells comprise a humanized a proliferation-inducing ligand gene. Non-human animals and cells that express a human or humanized a proliferation-inducing ligand protein from an endogenous a proliferation-inducing ligand locus are described.

Abstract: Non-human animals, cells, methods and compositions for making and using the same are provided, wherein the non-human animals and cells comprise a humanized B-cell activating factor gene. Non-human animals and cells that express a human or humanized B-cell activating factor protein from an endogenous B-cell activating factor locus are described.

Abstract: Non-human animals, cells, methods and compositions for making and using the same are provided, wherein the non-human animals and cells comprise a humanized a proliferation-inducing ligand gene. Non-human animals and cells that express a human or humanized a proliferation-inducing ligand protein from an endogenous a proliferation-inducing ligand locus are described.

Abstract: Compositions and methods are described for normalizing a bioluminescent signal in a live animal.

Abstract: Non-human animals, cells, methods and compositions for making and using the same are provided, wherein the non-human animals and cells comprise a humanized B-cell activating factor gene. Non-human animals and cells that express a human or humanized B-cell activating factor protein from an endogenous B-cell activating factor locus are described.

Abstract: In an aspect, the invention relates to a method of screening for a therapeutic for amyotrophic lateral sclerosis. In an aspect, the invention relates to transgenic Drosophila. In an aspect, the invention relates to a Drosophila model of amyotrophic lateral sclerosis. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: It was found that bacteria belonging to the genus Clostridium induce accumulation of regulatory T cells (Treg cells) in the colon. Moreover, the present inventors found that regulatory T cells (Treg cells) induced by from these bacteria suppressed proliferation of effector T-cells. From these findings, the present inventors found that the use of bacteria belonging to the genus Clostridium or a physiologically active substance derived therefrom made it possible to induce proliferation or accumulation of regulatory T cells (Treg cells), and further to suppress immune functions.

Abstract: Provided is a pterygium animal model produced by injecting human-derived pterygial epithelial cells that are isolated and cultured in vitro. The animal model has characteristics similar to those of pterygium, which are observed only in humans, wherein such characteristics are caused in such a way that pterygial epithelial cells are isolated from human pterygium corneal tissues and cultured, the cultured pterygial epithelial cells are sub-cultured, and human-derived pterygial epithelial cells of which identify is confirmed are injected into the nasal subconjunctival space of mice. The pterygium animal model allows a pterygium therapeutic agent to be effectively screened.

Abstract: The present invention relates to methods of treating and preventing Staphylococcus aureus infection and/or a condition resulting from a S. aureus infection a subject that involves administering a CD11b inhibitor. The present invention further relates to a non-human transgenic animal expressing human CD11b and its use in methods of identifying novel therapeutics for the treatment and prevention of Staphylococcus aureus infection and/or a condition resulting from a S. aureus infection.

Abstract: Methods of normalizing bile acid production in a mouse engrafted with human hepatocytes by the administration of human FGF19 are disclosed. Also disclosed is a transgenic host animal, such as a mouse, that expresses human FGF19 that has normalized bile acid production when engrafted with human hepatocytes.

Abstract: A method for changing a condition of an eyelid of a hairless animal, a model animal for evaluating a therapeutic or prophylactic effect against an eyelid disease obtained by the method, a method for producing the model animal, a method of screening using the model animal and a substance having a therapeutic or prophylactic effect against an eyelid disease selected by the method of screening, and a therapeutic or prophylactic agent against an eyelid disease containing the substance as an active ingredient.

Abstract: The present invention provides a mouse with liver damage, having a high degree of damage against the mouse's original hepatocytes while having a uPA gene in a heterozygous form, and a method for efficiently preparing the mouse. Specifically, the method for preparing a mouse with liver damage having the uPA gene in a heterozygous form comprises the following steps of: (i) transforming mouse ES cells with a DNA fragment containing a liver-specific promoter/enhancer and cDNA that encodes a urokinase-type plasminogen activator operably linked under the control thereof; (ii) injecting the transformed mouse ES cells obtained in step (i) into a host embryo; (iii) transplanting the host embryo obtained in step (ii) via the injection of the ES cells into the uterus of a surrogate mother mouse, so as to obtain a chimeric mouse; and (iv) crossing the chimeric mice obtained in step (iii), so as to obtain a transgenic mouse in which the DNA fragment is introduced in a heterozygous form.

Abstract: A method for changing a condition of an eyelid of a mammal excluding a human, a model animal for evaluating a therapeutic or prophylactic effect against an eyelid disease obtained by the method, a method for producing the model animal, a method of screening using the model animal and a substance having a therapeutic or prophylactic effect against an eyelid disease selected by the method of screening, and a therapeutic or prophylactic agent against an eyelid disease containing the substance as an active ingredient.

Abstract: The invention discloses novel model of transgenic mammal, a method of crossbreeding transgenic mammal and the use of the transgenic mammal for assessing prevention and/or treatment methods for cardiovascular and other diseases related to lipoprotein(a). The transgenic mammal expresses human apolipoprotein (a) (apo(a)) and human apolipoprotein B-100 (apo B-100) genes and produces human lipoprotein (a), apo (a) and apo B-100 and produces no vitamin C. This novel dual transgenic mammal is the ideal model for testing pharmaceutical compounds for efficacy and usefulness in the prevention and/or treatment of human diseases.

Abstract: The present invention provides a CD81 and OCLN double transgenic mouse and its construction method and use. The double transgenic mouse can be used to constitute acute and chronic HCV infection in a mouse model.