Abstract: Methods are disclosed herein for producing human hepatocytes from human induced pluripotent stem cells. Also provided are transgenic rats for the expansion of human hepatocytes, such as those produced using the methods disclosed herein.

Abstract: A method of treating cancer in a subject includes contacting an enriched population of T-cells obtained from cancer or tumor draining lymph nodes ex-vivo with: an anti-CD3 antibody, an anti-CD28 antibody, and/or functional fragments thereof, and optionally a VEGF inhibitor and/or an IL-2 receptor agonist, at amounts effective to activate and expand the T-cells and administering the activated and expanded T-cells to the subject.

Abstract: The instant disclosure relates to methods for converting mammalian definitive endoderm (DE) cells into specific tissue(s) or organ(s) through directed differentiation. In particular, the disclosure relates to formation of gastric fundus tissue and/or organoids formed from differentiated definitive endoderm.

Abstract: A method for the expansion of tumor-specific T-cells includes obtaining an enriched population of T-cells from a subject with cancer; and contacting the enriched population of T-cells ex-vivo with: (i) an anti-CD3 antibody, an anti-CD28 antibody, and/or functional fragments thereof, and (ii) a VEGF inhibitor, to activate and expand the T-cells.

Abstract: Sequences of a serotype 8 adeno-associated virus and vectors and host cells containing these sequences are provided. Also described are methods of using such host cells and vectors in production of rAAV particles.

Abstract: Provided herein are flu hemagglutinin polypeptides, including chimeric influenza virus hemagglutinin polypeptides, and flu hemagglutinin polypeptides comprising modified glycosylation sites and non-naturally glycosylation sites, compositions comprising the same, vaccines comprising the same and methods of their use.

Abstract: The invention provides fusion proteins comprising at least one fluorescent protein that is linked to at least one transporter protein that changes three-dimensional conformation upon specifically transporting its substrate. The transporter protein may be a nitrate transporter, a peptide transporter, or a hormone transporter. The invention provides fusion proteins comprising at least one fluorescent protein that is linked to at least one mechanosensitive ion channel protein. The invention also provides for methods of using the fusion proteins of the present invention and nucleic acids encoding the fusion proteins.

Abstract: The present invention involves the use of transcription factors including Tbx5, Mef2C, Hand2, myocardin and Gata4 to reprogram cardiac fibroblasts into cardiomyocytes, both in vitro and in vivo. Such methods find particular use in the treatment of patients post-myocardial infarction to prevent or limit scarring and to promote myocardial repair.

Abstract: The present invention provides nanoparticles and compositions of various constructs that combine meta-stable viral proteins (e.g., RSV F protein) and self-assembling molecules (e.g., ferritin, HSPs) such that the pre-fusion conformational state of these key viral proteins is preserved (and locked) along with the protein self-assembling into a polyhedral shape, thereby creating nanoparticles that are effective vaccine agents. The invention also provides nanoparticles comprising a viral fusion protein, or fragment or variant thereof, and a self-assembling molecule, and immunogenic and vaccine compositions including the same.

Abstract: A leucine zipper variant, a polynucleotide encoding the leucine zipper variant, a method of preparing a leucine zipper variant, a method of inhibiting HDM2- and/or HDMX using the leucine zipper variant, and a method of the prevention and/or treatment of cancer using the leucine zipper variant.

Abstract: The present invention relates to Huwentoxin-IV variants, polynucleotides encoding them, methods of making and using the foregoing, and methods of alleviating pain with peptide inhibitors of Nav1.7.

Abstract: Analyte sensors, methods for producing and using analyte sensors, methods of detecting and/or measuring analyte activity, detecting pH change, and/or, controlling the concentration of an analyte in a system, are disclosed. Embodiments of the analyte sensors according to the disclosure can provide an accurate and convenient method for characterizing analyte activity, detecting pH change, controlling the concentration of an analyte in a system, and the like, in both in vivo and in vitro environments, in particular in living cell imaging.

Abstract: Disclosed herein are methods for controlling stem cell differentiation through the introduction of transgenes having Xic, Tsix, Xite, or Xic flanking region sequences to block differentiation and the removal of the transgenes to allow differentiation. Also disclosed are small RNA molecules and methods for using the small RNA molecules to control stem cell differentiation. Also disclosed are stem cells genetically modified by the introduction of Xic, Tsix, XUe, or Xic flanking region sequences.

Abstract: The present invention provides further improved compositions and methods for efficient lysosomal targeting based on the GILT technology. Among other things, the present invention provides methods and compositions for targeting lysosomal enzymes to lysosomes using furin-resistant lysosomal targeting peptides. The present invention also provides methods and compositions for targeting lysosomal enzymes to lysosomes using a lysosomal targeting peptide that has reduced or diminished binding affinity for the insulin receptor.

Abstract: The present invention relates to a one-vector expression system comprising a sequence encoding two polypeptides, such as tyrosine hydroxylase (TH) and GTP-cyclohydrolase 1 (GCH1). The two polypeptides can be should preferentially be expressed at a ratio between 3:1 and 15:1, such as between 3:1 and 7:1. The invention is useful in the treatment of catecholamine deficient disorders, such as dopamine deficient disorders including but not limited to Parkinson's Disease. Moreover, the present invention provides a method to deliver the vector construct in order to limit the increased production of the catecholamine to the cells in need thereof.

Abstract: The present invention relates to mutated tissue plasminogen activators, and their use for treating thrombotic diseases.

Abstract: The present invention provides an intercellular protein delivery system comprising an engineered peptide (EP), composed of secretion part (SP) and nuclear translocation part (NTP), a functional or therapeutic protein (FP), cells that express the fusion proteins and cells that accept the fusion proteins. The system can be used in vivo or in vitro to sustainably supply proteins of interest for cellular reprogramming, cellular differentiation and cell-based protein therapies.

Abstract: The present invention provides a fibromodulin (FMOD) reprogrammed (FReP) cell and a method of making therefor, a culture medium therefor, and a supernatant thereof, and methods of making and using these.

Abstract: The disclosure relates to the field of human genetics, particularly the field of peripheral neuropathy, particularly inherited peripheral neuropathy. Specifically, the disclosure relates to methods and materials to detect hereditary peripheral neuropathy, more particularly autosomal recessive Charcot-Marie-Tooth disease.

Abstract: Methods and diagnostic agents for identification of subjects for cancer treatment with an anti-hyaluronan agent, such as a hyaluronan-degrading enzyme, are provided. Diagnostic agents for the detection and quantification of hyaluronan in a biological sample and monitoring cancer treatment with an anti-hyaluronan agent, for example a hyaluronan-degrading enzyme, are provided. Combinations and kits for use in practicing the methods also are provided.

Abstract: The present invention discloses the identification and isolation of novel MHC class II epitopes derived from the cancer antigen, NY ESO-1. The novel MHC class II epitopes from NY-EsO-1 are recognized by CD4+ T lymphocytes in an HLA class II restricted manner, in particular HLA-DR or HLA-DP restricted. The products of the gene are promising candidates for immunotherapeutic strategies for the prevention, treatment and diagnosis of patients with cancer.

Abstract: Provided herein are chimeric influenza hemagglutinin (HA) polypeptides, compositions comprising the same, vaccines comprising the same, and methods of their use.

Abstract: The present invention is directed to novel tissue protective peptides. The tissue protective peptides of the invention may bind to a tissue protective receptor complex. In particular, the present invention is drawn to tissue protective peptides derived from or sharing consensus sequences with portions of cytokine receptor ligands, including Erythropoietin (EPO), that are not involved in the binding of the ligand to the receptor complex, e.g., to the EPO receptor homodimer. Accordingly, the tissue protective peptides of the invention are derived from the amino acid sequences of regions of cytokine receptor ligands that are generally located on or within the region of the ligand protein that is opposite of the receptor complex, i.e., are generally derived from amino acid sequences of regions of the ligand protein that face away from the receptor complex while the ligand is bound to the receptor.

Abstract: Disclosed are methods of promoting and/or enhancing G-Protein Coupled Receptor (GPCR) localization to the cell membrane and/or cell surface; methods of promoting and/or enhancing GPCR functional expression; and methods and assays for screening or identifying ligands (e.g., agonists or antagonists) that bind GPCRs. Also provided are vectors, recombinant cells, and stable cell lines for use in the methods and assays.

Abstract: The present provides fusion proteins comprising PDGF and VEGF binding portions, and recombinant viral particles encoding the fusion proteins. Compositions comprising the fusion proteins and viral particles as well as methods of using the same are also provided.

Abstract: Disclosed are multi-chambered cell co-culture systems. The systems can be utilized to encourage the growth and development of isolated cells in a dynamic three-dimensional in vitro environment. The cell chambers (10) of the system can be in biochemical communication with adjacent chambers containing cells of different types, but the different cell types are maintained physically separated from one another. In addition, the local environment of each cell chamber can be independently controlled. For example, fluid flow characteristics through a single cell chamber can be independently controlled and maintained for each separate chamber of the system.

Abstract: The invention provides for systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are vectors and vector systems, some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for selecting specific cells by introducing precise mutations utilizing the CRISPR/Cas system.

Abstract: The present invention relates to a cell line in which an expression construct is introduced into a genomic DNA, the expression construct including: (a) a promoter operable in animal cells and heterologous to adenoviruses; and (b) a modified adenovirus E1 coding gene sequence of SEQ ID NO:1 operatively linked to the promoter. According to the present invention, the cell line of the present invention is a novel cell line which is less likely to produce a replication competent adenovirus (RCA). The adenovirus producing cell line of the present invention has a low possibility of producing RCA due to homologous recombination, when compared with conventional cell lines. Therefore, this makes it possible to regulate the required amount of virus during gene therapy using the adenovirus and prevent tissue damage and toxic effects caused by overproduction of the adenovirus.

Abstract: The present invention provides compositions comprising retroviral vectors, transduced cells, and methods of using the same for gene therapy. In particular, the present invention relates to lentiviral vectors and cells transduced with those vectors to provide gene therapy to subjects having an adrenoleukodystrophy and/or adrenomyeloneuropathy.

Abstract: The present invention relates to fibronectin-based scaffold domain proteins that bind to myostatin. The invention also relates to the use of these proteins in therapeutic applications to treat muscular dystrophy, cachexia, sarcopenia, osteoarthritis, osteoporosis, diabetes, obesity, COPD, chronic kidney disease, heart failure, myocardial infarction, and fibrosis. The invention further relates to cells comprising such proteins, polynucleotides encoding such proteins or fragments thereof, and to vectors comprising the polynucleotides encoding the proteins.

Abstract: The present invention refers to the gene cluster and genes comprised by the gene cluster which are involved in the biosynthesis of griselimycin and methylgriselimycin and to the use of the gene cluster, genes comprised thereby and proteins encoded thereby for the production of antibiotic agents.

Abstract: The present invention relates to fluorescent proteins, in particular green fluorescent proteins (GFPs), with increased activity in cells, and thus increased signal strength. A further aspect of the present invention relates to the use of peptides for increasing the expression and/or stability of a protein in a cell.

Abstract: The current disclosure provides a method for the creation of a high-density cryopreserved cell bank using perfusion culture techniques and non-centrifugal concentration of cells. Methods of production using this high-density cryopreserved cell bank are also provided.

Abstract: The present invention provides Fibroblast Growth Factor Receptor-Like (FGFR-L) polypeptides and nucleic acid molecules encoding the same. The invention also provides selective binding agents, vectors, host cells, and methods for producing FGFR-L polypeptides. The inventio further provides pharmaceutical compositions and methods for the diagnosis, treatment, amelioration, and/or prevention of diseases, disorders, and conditions associated with FGFR-L polypeptides.

Abstract: Disclosed herein are a light-inducible system and method for rapidly and reversibly modulating protein stability and function. This system and method employs conditionally stable protein domains that regulate the degradation of a fusion protein depending upon the presence or absence of a particular light source.

Abstract: Compounds are provided having inter alia good duration of action, high potency and/or convenient dosing regimens including oral administration, and reduced immunogenicity. The compounds are engineered polypeptides which incorporate an albumin binding domain in combination with one or more biologically active polypeptides. Also provided are pharmaceutical compositions and methods of treatment for diseases and disorders including obesity and overweight, diabetes, dyslipidemia, hyperlipidemia, Alzheimer's disease, fatty liver disease, Short Bowel Syndrome, Parkinson's disease, and cardiovascular disease.

Abstract: The present application provides novel human genes A7322, whose expression is markedly elevated in breast cancer. The present application also provides human genes F3374 whose expression is markedly elevated in breast cancer. These genes and polypeptides encoded thereby can be used, for example, in the diagnosis of breast cancer, and as target molecules for developing drugs against breast cancer. The invention features methods of screening for modulators of the kinase activity of PBK/TOPK. The invention further provides methods of screening for agents to prevent or treat cancer, such as breast cancer.

Abstract: Methods and cell lines for overexpressing functional gamma-carboxylated proteins are disclosed.

Abstract: The present invention relates to mutated tissue plasminogen activators, and their use for treating thrombotic diseases.

Abstract: The present invention provides methods of improving the levels and stability of expression of interleukin-12 family cytokine polypeptides by expressing the alpha and beta subunits of the polypeptides at their determined relative molar ratios that increase the levels and stability of expression of the heterodimer, e.g., in comparison to heterodimer expressed at an equimolar ratio.

Abstract: A vector production system is provided. The system comprises recombinant cells designed to encode at least a first recombinase under the control of an inducible promoter and the cells include an expression vector encoding a nucleic acid of interest within the regulatory elements of the expression vector which are flanked on either side by a target sequence for at least the first recombinase. The vector production system provides an efficient one-step process for producing linear or circular covalently closed vectors that incorporate a nucleic acid sequence of interest.

Abstract: The present invention provides variant activin IIB soluble receptor polypeptides and proteins capable of binding and inhibiting the activities of activin A, myostatin, or GDF-11. The present invention also provides polynucleotides, vectors and host cells capable of producing the variant polypeptides and proteins. Compositions and methods for treating muscle-wasting and other diseases and disorders are also provided.

Abstract: Disclosed is a composition for reprogramming somatic cells to generate embryonic stem cell-like cells, comprising: a) a Bmi1 (B cell-specific Moloney murine leukemia virus integration site 1) protein or a nucleic acid molecule coding for Bmi1; and b) an Oct4 protein or a nucleic acid molecule coding for Oct4. Also, a method is provided for reprogramming somatic cells to generate embryonic stem cell-like cells using the composition. In addition to reducing the number of the genetic factors conventionally needed, the composition and method allow the generation of pluripotent embryonic stem cell-like cells which have high potential in the cell therapy of various diseases.

Abstract: Human progenitor T cells that are able to successfully engraft a murine thymus and differentiate into mature human T and NK cells are described The human progenitor T cells have the phenotype CD34+CD7+CD1a?CD5? or CD34+CD7+CD1a?CD5+ and are derived from human hematopoietic stem cells, embryonic stem cells and induced pluripotent stem cells b\ coculture with cells expressing a Notch receptor ligand (OP9-DL1 or OP9-DL4) Such cells are useful in a variety of applications including immune reconstitution, the treatment of immunodeficiencies and as carriers for genes used in gene therapy.

Abstract: Described are methods for determining the permissiveness of a cell for a virus that is a member of the family Arteriviridae or Coronaviridae or Asfarviridae, in particular, for Porcine Reproductive and Respiratory Syndrome Virus (PRRSV). Further described are methods and compositions related to the generation of host cells permissive for a virus that is a member of the family Arteriviridae or Coronaviridae or Asfarviridae, in particular, for PRRSV. Methods of utilzing the cells thus identified or thus generated, in preparing a culture of a virus that is a member of the family Arteriviridae or Coronaviridae or Asfarviridae, as well as the use of the virus for the purpose of vaccine production or diagnosis, are also described.

Abstract: A basement membrane having a barrier function is formed by culturing alveolar epithelial cells or vascular endothelial cells on a fibrous collagen matrix coated with a polymer having a sugar chain that can localize a receptor that has an activity to accumulate a basement membrane component on the basal surface of the cells having an ability to form a basement membrane. A reconstructed artificial tissue is obtained by seeding and culturing desired homogeneous or heterogeneous cells on the basement membrane specimen constructed by the following process: (i) the cells having an ability to form a basement membrane adhered onto a support structure through a basement membrane are treated with a surface active agent; (ii) the lipid component of cells is lysed; (iii) the mixture of an alkaline solution and a protease inhibitor is used to lyse the protein remained on the surface of the basement membrane of the cells.

Abstract: The present invention relates in general to therapeutic fusion proteins useful to treat lysosomal storage diseases and methods for treating such diseases. Exemplary therapeutic fusion proteins comprise a lysosomal enzyme, a lysosomal targeting moiety, e.g., an IGF-II peptide, and a spacer peptide. Also provided are compositions and methods for treating Mucopolysaccharidosis Type IIIB (Sanfilippo B Syndrome), comprising a targeted therapeutic fusion protein comprising alpha-N-acetylglucosaminidase (Naglu), a lysosomal targeting moiety, e.g., an IGF-II peptide, and a spacer peptide.

Abstract: The present invention relates to a polypeptide binding to a chymase (EC 3, 4, 21,39), wherein the polypeptide comprises or consists of an amino acid sequence selected from the group consisting of: (a) GVTLFVALYDY(X1)A(X2)(X3)(X4)(X5) (X6)LSFHKGEKFQIL(X7 (X8)(X9)(X10) (X11)(X12)G(X13)(X14)WEARSLTTGETGYIPSNYVAPVDSIQ (SEQ ID NO: 1), wherein (X1) is R, N, Q, E, K, H, S, T, C, or D; (X2) is E, T, D, Q, L, P, A, S, C, M, N, E, G, A, V or I; (X3) is R, T, H, N, K, S, C, N or Q; (X4) is S, W, T, C, N, Q, For Y; (X5) is T, H, L, F, C, S, M, N, Q, R, K, G, A, V, I, P, Y or W; (X6) is D, Q, H, E, S, T, C, N, R or K; (X7) is D, N, R, E, Q, S, T, C, K or D; (X8) is M, W, G, F, A, S, T, C, S, N, Q, Y, V, L, I or P; (X9) is T, H, S, D, C, N, Q, R, K, E or absent; (X10) is V, T, Q, G, A, L, I, P, S, C, M, N or absent; (X11) is P, A, D, G, K, V, L, I, E, R, M, H or absent; (X12) is N, V, P, I, E, T, S, A, G, L, C, M, Q or D; (X13) is D, E, T, P, G, A, V, L, I, S, C, M, N or Q, and (X14) is W, Y, L, G, A, V, I, P, M, or F; (b)

Abstract: As discussed in greater detail herein, isolated epitope peptides derived from MPHOSPH1 bind to an HLA antigen and induce cytotoxic T lymphocytes (CTL) and thus are suitable for use in the context of cancer immunotherapy, more particularly cancer vaccines. The inventive peptides encompass both the above-mentioned MPHOSPH1-derived amino acid sequences and modified versions thereof, in which one, two, or several amino acids are substituted, deleted, inserted or added, provided such modified versions retain the requisite CTL inducibility of the original sequences. Further provided are polynucleotides encoding any of the aforementioned peptides as well as pharmaceutical agents or compositions that include any of the aforementioned peptides or polynucleotides.

Abstract: The present invention relates to polypeptides that bind to H3K4 methylated chromatin, and in particular to the use of reagents comprising such polypeptides for epigenetic/epigenomic analysis.