Abstract: The present disclosure provides a method for designing a set of guide RNAs for hybridizing a genomic region of interest. The present disclosure further provides methods of editing at least one genomic region of interest with at least one set of guide RNAs.

Abstract: A liver lesion-mouse model which is a liver-specific ISX gene expression and p53 gene knockout transgenic mouse, wherein liver lesion develops after the mouse is fed with a high calorie diet.

Abstract: The present invention concerns non-human animals with cells having a genome that is lacking the entire E3 ubiquitin ligase (Ube3a) gene (including all isoforms and alternative promoters). These animals are useful for modeling Angelman Syndrome. The invention also includes methods for assessing the effect of an agent, such as potential therapeutics, on an animal model by exposing the animal or cells, tissues, or organs isolated therefrom, to an agent of interest.

Abstract: Genetically modified non-human animals which are deficient in expression of an endogenous GPC3 polypeptide and express a human GPC3 polypeptide at a physiologically adequate level; methods for producing the non-human animals; and methods for evaluating test substances using the non-human animals. Furthermore, methods for evaluating test substances regarding their safety, therapeutic effects on diseases, pharmacokinetics, in vivo distribution, and such, using the non-human animals as models.

Abstract: Compositions and methods are described herein for transdifferentiation of multipotent stromal cells into cells that can express insulin.

Abstract: A mammalian cell comprising at least four distinct recombination target sites (RTS), an adenovirus (Ad) gene comprising E1A, E1B or a combination thereof, and a promoter operatively linked to the Ad gene, wherein the RTS, the Ad gene, and the promoter are chromosomally-integrated; methods for using the cell for generating a recombinant adeno-associated virus (rAAV) producer host cell; and methods for using the AAV producer host cell to produce, package and purify rAAV.

Abstract: A NOD.Cg-PrkdcscidH2rgtm1 Wjl/SzJ.(NOD-scid-IL2r?null, NSG) mouse which is genetically modified such that the en NSG mouse lacks functional major histocompatibility complex I (MHC I) and lacks functional major histocompatibility complex II (MHC II) is provided according to aspects of the present, invention. According to specific aspects the genetically modified NSG mouse, is a NOD.Cg-PrkdcscidH2-K1tml Bpe H2-Ab1eml Mvw H2-D1tml Bpe H2rgtm Wjl/SzJ (NSG-Kb Db)null(IAnull)) mouse, NSG-RIP-DTR (Kb Db)null(IAnull) mouse, or a NOD.Cg-B2mtmlUnePrKdcscidH2dlAb1-E?H2rgtm1 Wjl/SzJ (NSG-B2Mnull(IA IEnull)) mouse. Human, immune cells and/or human: tumor cells are administered to a genetically modified immunodeficient mouse according to aspects described herein and assays of one or more test substances can be performed using the provided mice.

Abstract: Genetically modified non-human animals are provided that may be used to model human hematopoietic cell development, function, or disease. The genetically modified non-human animals comprise a nucleic acid encoding human IL-6 operably linked to an IL-6 promoter. In some instances, the genetically modified non-human animal expressing human IL-6 also expresses at least one of human M-CSF, human IL-3, human GM-CSF, human SIRPa or human TPO. In some instances, the genetically modified non-human animal is immunodeficient. In some such instances, the genetically modified non-human animal is engrafted with healthy or diseased human hematopoietic cells. Also provided are methods for using the subject genetically modified non-human animals in modeling human hematopoietic cell development, function, and/or disease, as well as reagents and kits thereof that find use in making the subject genetically modified non-human animals and/or practicing the subject methods.

Abstract: The present invention provides a composition comprising dendritic cells loaded with hHsp60sp, which dendritic cells are from a subject and have been fixed with paraformaldehyde (PFA). The subject may suffer from an autoimmune disease. Also provided are a method for preparing the composition; recombinant human cells comprising a heterologous gene encoding a fusion protein of HLA-E and hHsp60sp or B7sp, and expressing the fusion protein on the surface of the cells; a method for determining a percentage of maximum inhibition of testing the function of the HLA-E restricted CD8+ Treg cells from a subject, determining whether HLA-E restricted CD8+ Treg cells freshly isolated from a subject are defective, or determining whether defective HLA-E restricted CD8+ Treg cells from a subject are correctable; and a method for correcting defective HLA-E restricted CD8+ Treg cells, treating type 1 diabetes (T1D), or treating multiple sclerosis (MS).

Abstract: Compositions and regimens useful in treating hemophilia A are provided. The compositions include recombinant adeno-associated virus (rAAV) with a transthyretin enhancer and promoter driving expression of a human Factor VIII.

Abstract: Spinal cord neural stem cells (NSCs) have great potential to reconstitute damaged spinal neural circuitry. In some embodiments, derivation of spinal cord NSCs from human pluripotent stem cells (hPSCs) is described. These spinal cord NSCs can differentiate into a diverse population of spinal cord neurons comprising multiple positions in the dorso-ventral axis, and can be maintained for prolonged time periods. After grafting into injured spinal cords, grafts may be rich with excitatory neurons, extend large numbers of axons over long distances, innervate their target structures, and enable robust corticospinal regeneration. In some embodiments, hPSC-derived spinal cord NSCs enable a broad range of biomedical applications for in vitro disease modeling, and can provide a clinically-translatable cell source for spinal cord “replacement” strategies in several spinal cord disorders.

Abstract: The present invention relates to a gene therapy vector which is useful in the treatment or prevention of hypertrophic cardiomyopathy in a subject in need thereof. The gene therapy vector of the invention comprises a nucleic acid sequence encoding a cardiac sarcomeric protein and a cardiomyocyte-specific promoter which is operably linked to said nucleic acid sequence. The invention furthermore relates to a cell which comprises the gene therapy vector. Pharmaceutical compositions which comprise the gene therapy vector and/or a cell comprising said vector are also provided. In another aspect, the invention relates to a method for treating or preventing hypertrophic cardiomyopathy in a subject by introducing the gene therapy vector of the invention into a subject in need of treatment.

Abstract: The present invention is in the field of pluripotent stem cells, more particularly cardiomyocytes derived from pluripotent stem cells. The present invention provides a novel method for differentiating human pluripotent stem cells into a population of cardiomyocytes having an atrial phenotype, and use of said atrial cardiomyocytes for screening of drugs, AF disease model, and others. The method of the invention is particularly useful to generate cardiomyocytes having a more developed or mature atrialphenotype and/or to generate higher yield of cardiomyocytes having an atrialphenotype.

Abstract: Disclosed herein are methods for the in vitro differentiation of a precursor cell into definitive endoderm, which may further be differentiated into a human colonic organoid (HCO), via modulation of signaling pathways. Further disclosed are HCOs and methods of using HCOs, which may be used, for example, for the HCOs may be used to determine the efficacy and/or toxicity of a potential therapeutic agent for a disease selected from colitis, colon cancer, polyposis syndromes, and/or irritable bowel syndrome.

Abstract: The present invention relates to compositions and methods, in particular to methods based on systemic injection of rAAV, for delivering genes to cells of the central nervous system in mammals, such as brain neurons or glial cells, and in particular to motor neurons or glial cells of the spinal cord The invention also relates to methods of treating motor neuron disorders in mammals by expression of therapeutic genes. The invention stems from the unexpected discovery that peripheral injection of AAV vectors leads to a bypass of the blood brain barrier and a massive infection of motor neurons. The invention may be used in any mammal, including human subjects.

Abstract: Described herein are methods, compositions, and kits for directed differentiation of human pluripotent stem cells, neuromesodermal progenitors, and neural stem cells into biomimetic neural tissues comprising one or more rosette structures. Preferably, the methods provided herein direct differentiation of human pluripotent stem cells, neuromesodermal progenitors, and neural stem cells into biomimetic neural tissues comprising a singular neural rosette structure that is comparable to at least a portion of the developing human neural tube. Also described are engineered neural tissue preparations comprising biomimetic neural tissues comprising a singular rosette structure having regional neural progenitor phenotypes.

Abstract: The present invention relates to an expression system for the heterologous expression of a nucleic acid sequence of interest in a mammalian cell, the system comprising: (i) a first genetic entity, comprising: a nucleic acid sequence encoding a functional Epstein Barr virus nuclear antigen 1 (EBNA-1), the nucleic acid sequence being operably linked to regulatory elements that allow for expression of the nucleic acid sequence encoding a functional EBNA-1; (ii) a second genetic entity, comprising: a nucleic acid sequence encoding a functional nucleoside diphosphate kinase A (NDPK-A), the nucleic acid sequence being operably linked to regulatory elements that allow for expression of the nucleic acid sequence encoding a functional NDPK-A; (iii) a third genetic entity, comprising: the nucleic acid sequence of interest being operably linked to regulatory elements that allow for expression of the nucleic acid sequence of interest; and (iv) a four genetic entity, comprising: the Epstein Barr virus OriP sequence or one

Abstract: Disclosed herein are cell cultures comprising PDX1-positive endoderm cells and methods of producing the same. Also disclosed herein are cell populations comprising substantially purified PDX1-positive endoderm cells as well as methods for enriching, isolating and purifying PDX1-positive endoderm cells from other cell types. Methods of identifying differentiation factors capable of promoting the differentiation of endoderm cells, such as PDX1-positive foregut endoderm cells and PDX1-negative definitive endoderm cells, are also disclosed.

Abstract: An object of the present invention is to provide an endodermal cell population for obtaining optimal somatic cells as cell therapy preparations. The endodermal cell population of the present invention has a reduced content proportion of undifferentiated cells in the cell population and contains endodermal cells differentiable into optimal somatic cells as cell therapy preparations. Further, a somatic cell derived from the endodermal cell population of the present invention has excellent therapeutic effects as a cell therapy preparation.

Abstract: An organ container includes a bottomed tubular outer container and a bottomed tubular inner container that is fitted into the outer container. A fluid flow path is formed between an outer peripheral surface of the inner container and an inner peripheral surface of the outer container. The outer container has an inlet that communicates between the fluid flow path and the outside, and an outlet that communicates between the fluid flow path and the outside.