Abstract: Provided herein are antisense agents for knocking down, inhibiting, or silencing expression of an HNF4?-P2 isoform mRNA in a cell or a patient. Also provided are methods of knocking down, inhibiting, or silencing expression of an HNF4?-P2 isoform mRNA in a cell or a patient and methods of treating a patient with liver disease, liver damage, liver inflammation, or liver failure, such as acute liver failure, ALD, AH, or ACLF.

Abstract: The present invention discloses a system for targeted gene editing and related uses.

Abstract: The present invention relates to in vitro expression of proteins and particularly, although not exclusively, to expression of proteins in mammalian cell lines. In particular, the present invention relates to the provision of a novel vector for protein expression, and methods of using such vector in the expression of proteins in mammalian cell lines.

Abstract: Methods are provided for the cell-based delivery of collagen VII for the treatment of Epidermolysis Bullosa and corneal erosion. The disclosure also provides a composition and a pharmaceutical composition comprises, comprise, or alternatively consist essentially of, or yet further consist of a keratinocyte sheet or a corneal cell sheet.

Abstract: The object of the present invention is to find a pharmaceutical having strong cancer therapeutic effect. The present invention provides a pharmaceutical composition for cancer therapy comprising a transcription or processing product of a gene encoding a miRNA, wherein said miRNA is one or more miRNAs selected from the group consisting of miR-3140, miR-137, miR-631, and miR-657, pharmaceutical composition.

Abstract: Some aspects of this disclosure provide strategies, systems, reagents, methods, and kits that are useful for engineering Cas9 and Cas9 variants that have increased activity on target sequences that do not contain the canonical PAM sequence. In some embodiments, fusion proteins comprising such Cas9 variants and nucleic acid editing domains, e.g., deaminase domains, are provided.

Abstract: The present invention is directed to genome editing systems, reagents and methods for immunooncology.

Abstract: The present invention pertains to methods and compounds useful in a therapy involving the administration of immune cells to a patient. The method of the invention involves the modification of cells of the immune system with agonists or antagonists of immune regulators such as Interleukin-10 (IL-10) or IL-6, in order to enhance and improve the immunological potential of the immune cells for therapy. Cells modified according to the method of the invention can be administered to a patient to support a treatment of proliferative diseases such as cancer or autoimmune disorders.

Abstract: Described herein are reprogrammed cells, and methods for cell dedifferentiation, transformation and eukaryotic cell reprogramming. Also described are cells, cell lines, and tissues that can be transplanted in a patient after steps of in vitro dedifferentiation and in vitro reprogramming. In particular embodiments the cells are Stem-Like Cells (SLCs), including Neural Stem-Like Cells (NSLCs), Cardiac Stem-Like Cells (CSLC), Hematopoietic Stem-Like Cells (HSLC), Pancreatic Progenitor-Like Cells, and Mesendoderm-like Cells. Also described are methods for generating these cells from human somatic cells and other types of cells. Also provided are compositions and methods of using of the cells so generated in human therapy and in other areas.

Abstract: A subject information acquisition unit calculates a bone mineral density in the bone region and a muscle mass in the soft region for each pixel on the basis of a radiographic image. A statistical value calculation unit calculates a statistical value related to the subject on the basis of the bone mineral density and the muscle mass. An evaluation value calculation unit calculates the fracture risk evaluation value for evaluating the fracture risk of the subject on the basis of the statistical value.

Abstract: The present disclosure relates to wound treatment and therapy and the promotion of tissue regeneration following injury. In particular, it relates to a microRNA-146a and nanoceria conjugate for improving wound healing and, in some embodiments, preventing adverse ventricular remodeling following myocardial infarction.

Abstract: The present disclosure is directed to methods and compositions for inhibiting a cancer cell using nucleic acid sequences encoding elephant p53 or elephant p53 amino acid sequences.

Abstract: Provided relates to the field of genetic engineering. In particular, a method for base editing in plant is provided. More specifically, a highly efficient A to G base editing method for a target sequence in a genome of a plant (e.g., a crop plant) by a guide RNA-directed CRISPR-adenine deaminase fusion protein and the plant and their progeny produced by the method are provided.

Abstract: The present invention relates to compositions and methods for increasing the rate of site specific insertion of a donor DNA sequence to the genome. More specifically, the method introduces a donor DNA template containing at least one transcription factor binding site to a cell in order to favor specific insertion of a donor template sequence at a target site by homology directed repair (HDR).

Abstract: Disclosed herein are T cell receptors (TCRs) capable of binding an antigen expressed by renal cell carcinoma cells. In some examples, the TCRs include an ? chain (such as SEQ ID NO: 2) and a ? chain (such as SEQ ID NO: 3). Also disclosed herein are vectors including nucleic acids encoding the disclosed TCR ? and/or ? chains. Further disclosed are modified T cells expressing the TCRs. In some examples, the modified T cells are prepared by transducing T cells with a vector including nucleic acids encoding the TCR ? chain and the TCR ? chain. In some embodiments, methods include treating a subject with RCC, by obtaining a population of T cells, transducing the population of T cells with a vector including a nucleic acids encoding the TCR ? chain and the TCR ? chain, and administering a composition comprising the modified T cells to the subject.

Abstract: The present disclosure is broadly concerned with the field of cancer immunotherapy. For example, the present invention generally relates to an immune cell comprising a genetically engineered antigen receptor that specifically binds to a target antigen and a genetic disruption agent that reduces or is capable of reducing the expression in the immune cell of a gene that weakens the function of the immune cell.

Abstract: Bispecific antibodies (bsAbs) have emerged as a class of promising anti-cancer and anti-infection biological drugs. They are capable of killing target cells, either cancer cells or microbe-infected cells, at levels of nanograms per milliliter serum in vivo, about 1e+5 folds more powerful than regular antibodies. To bypass the problems of high cost in production and inconvenience in administration, a logical solution is to use gene therapy vectors to produce them in vivo. In a series of preclinical studies, we have demonstrated that DNA MiniCircle was able to express far above therapeutic levels of bsAB persistently both in the presence as well as the absence of transfection co-factors. As a specific and intended improvement of the claimed invention, an enhanced form of bispecific antibodies incorporating a target cell-effector cell bridging device (BTEC) is additionally disclosed.

Abstract: The present invention relates to the use of a recombinant LAG-3 or derivatives thereof in order to boost a monocyte-mediated immune response, in particular to elicit an increase in the number of monocytes in blood. This finds use in the development of novel therapeutic agents for the treatment of an infectious disease or cancer.

Abstract: Described herein are methods and compositions related to generation of induced pluripotent stem cells (iPSCs). Improved techniques for establishing highly efficient, reproducible reprogramming using non-integrating episomal plasmid vectors. Using the described reprogramming protocol, one is able to consistently reprogram non-T cells with close to 100% success from non-T cell or non-B cell sources. Further advantages include use of a defined reprogramming media E7 and using defined clinically compatible substrate recombinant human L-521. Generation of iPSCs from these blood cell sources allows for recapitulation of the entire genomic repertoire, preservation of genomic fidelity and enhanced genomic stability.

Abstract: This disclosure related to modular and programmable peptide-oligonucleotide chimeras comprising of peptide and oligonucleotide segments interlinked by an organic core are presented and their assembly as morphologically-tunable soft materials, for example, nanostructure compositions comprising a plurality of compounds comprising a peptide segment and an oligonucleotide segment interlinked by an organic core moiety.

Abstract: Methods and compositions for a genetic disease are provided.

Abstract: In certain aspects, the present invention provides methods for inducing a stable gene modification of a target nucleic acid via homologous recombination in a primary cell, such as a primary blood cell and/or a primary mesenchymal cell. In certain other aspects, the present invention provides methods for enriching a population of genetically modified primary cells having targeted integration at a target nucleic acid. The methods of the present invention rely on the introduction of a DNA nuclease such as a Cas polypeptide and a homologous donor adeno-associated viral (AAV) vector into the primary cell to mediate targeted integration of the target nucleic acid. Also provided herein are methods for preventing or treating a disease in a subject in need thereof by administering to the subject any of the genetically modified primary cells or pharmaceutical compositions described herein to prevent the disease or ameliorate one or more symptoms of the disease.

Abstract: Methods and systems for autoinduction of gene expression, without the need to add exogenous inducers. A dual genetic element system, which includes a first, high copy number genetic element comprising a first gene of interest that is under the control of an inducible promoter, and a second, low copy number genetic element comprising a gene encoding a transcriptional factor which, upon expression, regulates transcription from the inducible promoter, wherein activation of transcription from the inducible promoter does not require addition of an exogenous inducer.

Abstract: The present invention discloses a system for targeted gene editing and related uses.

Abstract: The present invention relates to improved transposase polypeptides having increased solubility. The enzyme of the invention was developed based on the Sleeping Beauty (SB) transposase. The invention provides further nucleic acids, vectors and recombinant cells encoding or containing the improved transposase, as well as a transposase system. Furthermore provided are medical and non-medical uses of the transposase of the invention for gene delivery. The invention is in particular useful as a tool for gene delivery in genetically modified cell based therapeutic approaches for treating various diseases.

Abstract: A stage device capable of performing piercing vibration and translational driving by using one actuator, and performing very low-speed driving in the translational driving with high accuracy. The stage device includes an X stage having a vibration actuator that includes an vibration element and a contact body, one of which is a movable body connected to an object to be driven, and drives the object to be driven in an X-axis direction, and a control section that controls driving of the vibration actuator. The control section causes two-phase AC voltages to be applied to an electromechanical energy conversion element to thereby excite predetermined vibrations in the vibration element, to drive the vibration actuator by switching between a movement mode for moving the object to be driven in the X-axis direction and a vibration mode for vibrating the object to be driven in the X-axis direction.

Abstract: The present invention discloses a system for targeted gene editing and related uses.

Abstract: The present invention relates to plasma-based films and in particular to flexible plasma-based films. The invention further relates to and to methods of making and using the flexible plasma-based films. Embodiments of the invention have been particularly developed for making flexible plasma-based films useful as a hemostat in the treatment and/or prevention of mild to severe as well as arterial bleedings, as an anti-adhesive sheet to reduce or prevent development of surgery-induced adhesions, as a wound healing patch, as a wound dressing, or as a film useful in hernia repair. Embodiments of the invention will be described hereinafter with reference to these applications. However, it will be appreciated that the invention is not limited to this particular field of use.

Abstract: Disclosed herein are kits comprising transcription factors for inducing a fibroblast cell into an induced embryonic neural progenitor cell. The induced embryonic neural progenitor cell is then capable of differentiating into an astrocyte, an oligodendrocyte or a neuron. Also disclosed are the uses of the kit as a platform for selecting a drug candidate to treat neurological diseases.

Abstract: Disclosed herein are compositions and methods for cell therapy comprising an engineered cell. The present invention is directed to a composition for treating a subject having or suspected of having a disease, the composition comprising a modified cell comprising a modified endogenous gene, wherein an endogenous gene or fragment thereof is replaced with a transgene using a CRISPR/Cas9 system to generate the modified endogenous gene, the modified cell having an altered response to a cell signal or stimulus.

Abstract: The object of the present invention is to find a pharmaceutical having strong cancer therapeutic effect. The present invention provides a pharmaceutical composition for cancer therapy comprising a transcription or processing product of a gene encoding a miRNA, wherein said miRNA is one or more miRNAs selected from the group consisting of miR-3140, miR-137, miR-631, and miR-657, pharmaceutical composition.

Abstract: Compositions and methods of the invention are directed to the formation and use of teratoma-derived skeletal muscle stem cells. In one embodiment, the teratoma-derived skeletal muscle stem cells improve muscle contractile force (definition “functional”) when administered to a patient in need thereof.

Abstract: Methods of substantially retaining or otherwise preserving the biological activity of a dsRNA, present in a cell, to post-transcriptionally silence the expression of a gene in a target organism, comprising the step of adding to the cell composition a compound having the function of a protein—or amine—cross linking agent and/or an acid, and compositions comprising the cells comprising dsRNA, and protein cross linking agents and/or acids, as well as the use of the cross linking agents and/or acids in the method.

Abstract: Provided herein are methods for transducing a plurality of cells in a composition of cells, such as a population of lymphocytes, containing viral particles. In some aspects, provided methods and reagents for the transduction of cell populations involve binding of agents to a molecule on the surface of the cells. In some cases, the reagents are multimerization reagents and the one or more agents are multimerized by reversibly binding to the reagent. In some aspects, the multimerized agent can provide for transduction and/or expansion or proliferation or other stimulation of a population of cells, and then such agents can be removed by disruption of the reversible bond. Also provided are compositions, apparatus and methods of use thereof.

Abstract: Provided is a method for inducing a skeletal muscle cell including a step of introducing MyoD family gene or an expression product thereof and Myc family gene or an expression product thereof into a somatic cell of a mammal.

Abstract: The invention includes chitosan nanofibers having enhanced structural integrity, compositions comprising such chitosan nanofibers, and related methods of use. In a particular aspect, electrospun chitosan nanofibers can be reversibly acylated to enhance structural integrity and promote healing and the formation of tissues in a subject. In another aspect, electrospun chitosan nanofibers comprising at least a portion of the amino groups protected, such as through N-tert-butoxycarbonyl groups, demonstrate enhanced structural integrity and promote healing and the formation of tissues in a subject. The invention also includes compositions and methods for producing a modified chitosan material having anti-inflammatory and pro-healing characteristics and methods of using the modified chitosan materials in a film, a gel, a membrane, microfibers, nanofibers, nano- or micro-particles/spheres and/or sponges. In some aspects, microspheres and methods of producing microspheres comprising modified chitosan are included.

Abstract: Embodiments of the present disclosure can include a method for convective intracellular delivery including providing cells and molecules to a microchannel having compressive surfaces, wherein the compressive surfaces define compression gaps having a height of from 20 and 80% of the average cell diameter; and a plurality of relaxation spaces disposed between the compressive surfaces; flowing the cell medium through the microchannel, wherein as the cell medium flows through the microchannel, the plurality of cells undergo a convective intracellular delivery process comprising: compressing the plurality of cells, wherein the compressing causes the plurality of cells to undergo a loss in intracellular volume (Vloss); and passing the plurality of cells to a first relaxation space, wherein the plurality of cells undergo a gain in volume (Vgain) and absorb a portion of the plurality of molecules.

Abstract: Provided is an isolated population of human pluripotent stem cells comprising at least 50% human pluripotent stem cells characterized by an OCT4+/TRA1-60?/TRA1-81?/SSEA1+/SSEA4? expression signature, and novel methods of generating and maintaining same in a pluripotent, undifferentiated state a suspension culture devoid of cell clumps. Also provided are novel culture media, cell cultures and methods for culturing pluripotent stem cells in a suspension culture or a two-dimensional culture system while maintaining the cells in a proliferative, pluripotent and undifferentiated state. The novel culture media comprise interleukin 11 (IL11) and Ciliary Neurotrophic Factor (CNTF); bFGF at a concentration of at least 50 ng/ml and an IL6RIL6 chimera; or an animal contaminant-free serum replacement and an IL6RIL6 chimera. Also provided are methods for generating lineage-specific cells from the pluripotent stem cells.

Abstract: The present disclosure relates to a medium composition for r25/eprogramming induced pluripotent stem cells, containing an Ecklonia cava extract. Also, the present disclosure relates to a method for manufacturing induced pluripotent stem cells by using the medium composition. When the medium composition according to the present disclosure is used, induced pluripotent stem cells can be efficiently produced using adipose-derived mesenchymal stem cells safely and easily. The manufactured pluripotent stem cells are differentiable into various cells, and thus can be favorably used as a cell therapeutic agent.

Abstract: Methods for producing new neurons in the brain in vivo are provided according to aspects of the present invention which include introducing NeuroD1 into a glial cell, particularly into a reactive astrocyte or NG2 cell, thereby “converting” the reactive glial cell to a neuron. Methods of producing a neuronal phenotype in a glial cell are provided according to aspects of the present invention which include expressing exogenous NeuroD1 in the glial cell, wherein expressing exogenous NeuroD1 includes delivering an expression vector, such as a viral expression vector, including a nucleic acid encoding the exogenous NeuroD1 to the glial cell.

Abstract: The invention relates to an artificial nucleic acid molecule comprising an open reading frame and a 3?-UTR comprising at least one poly(A) sequence or a polyadenylation signal. The invention further relates to a vector comprising the artificial nucleic acid molecule comprising an open reading frame and a 3?-UTR comprising at least one poly(A) sequence or a polyadenylation signal, to a cell comprising the artificial nucleic acid molecule or the vector, to a pharmaceutical composition comprising the artificial nucleic acid molecule or the vector and to a kit comprising the artificial nucleic acid molecule, the vector and/or the pharmaceutical composition. The invention also relates to a method for increasing protein production from an artificial nucleic acid molecule and to the use of a 3?-UTR for a method for increasing protein production from an artificial nucleic acid molecule.

Abstract: Compositions and methods for enhancing targeted gene editing and methods of use thereof are disclosed. In the most preferred embodiments, gene editing is carried out utilizing a gene editing composition such as triplex-forming oligonucleotides, CRISPR, zinc finger nucleases, TALENS, or others, in combination with a gene modification potentiating agent such as stem cell factor (SCF), a CHK1 or ATR inhibitor, or a combination thereof. A particular preferred gene editing composition is triplex-forming peptide nucleic acids (PNAs) substituted at the ? position for increased DNA binding affinity. Nanoparticle compositions for intracellular delivery of the gene editing composition are also provided and particular advantageous for use with in vivo applications.

Abstract: Non-human animals, and methods and compositions for making and using the same, are provided, wherein the non-human animals comprise a humanization of a Lymphocyte activation gene 3 (Lag3). The non-human animals may be described, in some embodiments, as having a genetic modification to an endogenous Lag3 locus so that the non-human animals express a Lag3 polypeptide that includes a human portion and an endogenous portion (e.g., a non-human portion).

Abstract: The invention provides a method for generating a transgenic eukaryotic cell population having a modified human Rosa26 locus, which method includes introducing a functional DNA sequence into the human Rosa26 locus of starting eukaryotic cells. Also provided are targeting vectors useful in the method, as well as a cell population and a transgenic non-human animal comprising a modified human Rosa26 locus. Finally, the invention provides an isolated DNA sequence corresponding to the human Rosa26 locus.

Abstract: A process for producing a bone construct, including the steps of providing a perfusion bioreactor having an inlet and an outlet; providing the perfusion bioreactor with a seeded scaffold comprising a porous scaffold seeded with mesenchymal stem cells; continuously perfusing the seeded scaffold with an osteogenic induction (differentiation) media; measuring dissolved oxygen content of the osteogenic induction media at the inlet and at the outlet to determine an oxygen uptake rate (OUR) for the seeded scaffold; measuring glucose content of the osteogenic induction media to determine a glucose consumption rate (GCR) for the seeded scaffold; and removing the seeded scaffold from the perfusion reactor as a bone construct after the ratio of the OUR to the GCR (OUR/GCR) has been determined to exceed a predetermined threshold OUR/GCR value.

Abstract: The invention provides, inter alia, recombinase-based systems that provide for integrated logic and memory in living cells such as mammalian cells. The nucleic acid cassettes, switches, and systems described herein allow for control of gene expression or gene regulation. The invention also provides nucleic acid-based switches for adopted T-cell therapy.

Abstract: This invention provides expressible polynucleotides, which can express a target protein or polypeptide. Synthetic mRNA constructs for producing a protein or polypeptide can contain one or more 5? UTRs, where a 5? UTR may be expressed by a gene of a plant. In some embodiments, a 5? UTR may be expressed by a gene of a member of Arabidopsis genus. The synthetic mRNA constructs can be used as pharmaceutical agents for expressing a target protein or polypeptide in vivo.

Abstract: Disclosed herein are methods of generating induced pluripotent stem cells. The method involves providing a quantity of somatic or non-embryonic cells, contacting the contacting the somatic or non-embryonic cells with a quantity of one or more reprogramming factors and one or more RNA molecules, and culturing the somatic or non-embryonic cells for a period of time sufficient to generate at least one induced pluripotent stem cell. Various reprogramming factors and RNA molecules for use in the methods are disclosed herein. Also disclosed are cell lines and pharmaceutical compositions generated by use of the methods.

Abstract: The present invention relates to the field of genetic engineering, in particular, to a transposon-based transfection kit suitable for transfection of primary cells, such as T cells, comprising mRNA encoding a transposase, or reagents for generating mRNA encoding said transposase, as well as minicircle DNA comprising the transposon. The invention also relates to a nucleic acid, preferably, a DNA minicircle, comprising a transposon, wherein the transposon encodes a protein and at least one miRNA, wherein the sequences encoding the miRNA are located in an intron and expression of the protein and the miRNA is regulated by the same promoter. The invention also provides a population of cells obtainable with the method of the invention. Methods of transfection are also provided, as well as medical use, e.g. in immunotherapy, in particular, in adoptive T cell therapy or T cell receptor (TCR) or chimeric antigen receptor (CAR) gene therapy.

Abstract: A method of modulating some or all copies of a gene in a cell is provided including introducing into a cell one or more ribonucleic acid (RNA) sequences that comprise a portion that is complementary to all or a portion of each of the one or more target nucleic acid sequences, and a nucleic acid sequence that encodes a Cas protein and maintaining the cells under conditions in which the Cas protein is expressed and the Cas protein binds and modulates the one or more target nucleic acid sequences in the cell.