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 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 female germline stem cells and their progenitors, methods of isolation thereof, and methods of use thereof.

Abstract: The present invention is directed generally to eukaryotic cells comprising single-celled organisms that are introduced into the eukaryotic cell through human intervention and which transfer to daughter cells of the eukaryotic cell through at least five cell divisions, and methods of introducing such single-celled organisms into eukaryotic cells. The invention also provides methods of using such eukaryotic cells. The invention further provides single-celled organisms that introduce a phenotype to eukaryotic cells that is maintained in daughter cells. The invention additionally provides eukaryotic cells containing magnetotactic bacteria.

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: A composition and method for in vitro fertilization is provided which uses culture media comprising elevated concentrations of lipoic acid. More specifically, the invention provides culture media for developmental cells having a lipoic acid concentration of 5 ?M to 40 ?M. Culture media that include lipoic acid at concentrations within the identified range are able to provide blastocysts with increased survival, increased cell numbers, increased inner cell masses and/or increased percentage of the total mass made up by the inner cell compared to blastocysts cultured in a control medium.

Abstract: The present invention relates to methods for detecting for the presence of an agent that putatively causes or potentiates DNA damage comprising subjecting a cell (containing a DNA sequence encoding Gaussia luciferase (GLuc) reporter protein operatively linked to a human GADD45? gene promoter and a human GADD45? gene regulatory element arranged to activate expression of the DNA sequence in response to DNA damage) to an agent; and monitoring the expression of the GLuc reporter protein from the cell. The invention also concerns expression cassettes, vectors and cells which may be used according to such a method and also modified media that may be employed in assays and in preferred embodiments of the method of the invention.

Abstract: Provided are pro-coagulant compounds (e.g., pro-coagulant peptides or peptide derivatives) and methods of using and making those compounds. Further provided are conjugates between a pro-coagulant compound of the present disclosure (e.g., pro-coagulant peptide or peptide derivative) and a polypeptide selected from FIX, FVIIa, FVIII, and platelet targeting moieties (e.g., PDG-13), wherein the compound is linked to the polypeptide optionally via a linker. The compounds and conjugates are useful for the treatment of coagulation disorders, such as hemophilia A and hemophilia B. Further provided are methods of using and making the conjugates.

Abstract: The present invention relates to a method for preparing commercial scale quantities of human functional beta cells and to the establishment of cell lines from non-foetal pancreatic tissues. It also relates to a method of diagnosis using beta cell tumors or cells derived thereof. The method comprises sub-transplantation procedure to enrich the graft in proliferating beta cells, allowing to generate human Beta cell lines. Such lines express, produce and secrete insulin upon glucose stimulation. They have a gene expression profile that resembles to adult beta cells. In addition, the human beta cell lines are able to normalize glycemia of diabetic mice when transplanted, demonstrating their insulin secretion capabilities.

Abstract: The application provides products, which may trigger pro-apoptotic or pro-death effects on neoplastic cells and/or tissues of the human nervous system, more particularly on neoplastic cells and/or tissues of the human CNS. The products of the application can be used as anti-proliferative or tumoricid agents in the treatment and/or palliation and/or prevention of neoplasms of the human nervous system, more particularly of glioblastoma or brain stem glioma. Therefore, the application also relates to compositions, such as pharmaceutical compositions or drugs, which comprise at least one of said products, as well as to the biotechnological and medical applications of said products and compositions.

Abstract: The present disclosure provides method of generating cardiomyocytes from post-natal fibroblasts. The present disclosure further provides cells and compositions for use in generating cardiomyocytes.

Abstract: The methods of the present application describe that introduction of physiologically relevant miRNAs can enhance or modulate somatic cell reprogramming, generating induced pluripotent stem cells (iPS cells). These miRNAs did not further enhance reprogramming in the presence of cMyc. Furthermore, unlike previously described methods of generating iPS cells, such as through the introduction of genetic elements using viruses, the methods of the present invention reduce the risk of activating oncogenes in the iPS cells. The methods of the invention generate iPS cells that can be free of genetic modifications and thus have greater potential for use as therapeutic agents than those generated by existing methods.

Abstract: Avicins and other thioesterification agents are used to modify cysteine groups of signaling proteins in order to modify their activity. Pathologies associated with signaling proteins which are regulatable through this method are treated using these thioesterification agents. These pathologies include those involving proteins which modulate physiologic redox status of organisms including arthersclerosis, cancer, bacterial infection, inflammation, and neurological disorders.

Abstract: According to embodiments, a method of producing insulin-producing tissues (IPTs) by culturing comprises: preparing non-endocrinal epithelial cells (NEECs) and vascular endothelial cells (VECs), which have been isolated or originated from postnatal pancreata, preferably by capturing of NEECs by collagen; culturing in vitro the NEECs and the VECs at least partly separately from each other; and then generating in vitro a tissue complex (IPTs) that contains both the NEECs and the VECs. In another embodiment, the native islet cells are seeded on a monolayer of VECs that have preferably been separately cultured and purified. In a further embodiment, a method of enriching NEECs comprises: culturing NEECs adhering to a container or substrate; removing NEECs by treating with a tissue-dissociation enzyme to leave left-over cells (LOCs) still attached on the container or substrate; and culturing NEECs in a medium conditioned by, or in the presence of the LOCs.

Abstract: Disclosed are compositions and methods for method of treating a subject having reduced cardiac function or cardiac disease by administering adult bone marrow-derived stem cells to an individual. In some embodiments, the subject is a myocardial infarction patient or congestive heart failure patient. These cells can be administered as a liquid injectable or as a preparation of cells in a matrix which is or becomes solid or semi-solid. The cells can be genetically modified to enhance myocardial differentiation and integration. Also disclosed is a method for replacing cells ex vivo in a heart valve for implantation.

Abstract: A clustered regularly interspaced short palindromic repeat (CRISPR)-associated complex for adaptive antiviral defence (Cascade); the Cascade protein complex comprising at least CRISPR-associated protein subunits Cas7, Cas5 and Cas6 which includes at least one subunit with an additional amino acid sequence possessing nucleic acid or chromatin modifying, visualising, transcription activating or transcription repressing activity. The Cascade complex with additional activity is combined with an RNA molecule to produce a ribonucleoprotein complex. The RNA molecule is selected to have substantial complementarity to a target sequence. Targeted ribonucleoproteins can be used as genetic engineering tools for precise cutting of nucleic acids in homologous recombination, non-homologous end joining, gene modification, gene integration, mutation repair or for their visualisation, transcriptional activation or repression.

Abstract: This invention relates to methods for improved cell-based therapies for retinal degeneration and for differentiating human embryonic stem cells and human embryo-derived into retinal pigment epithelium (RPE) cells and other retinal progenitor cells.

Abstract: Methods and compositions for reducing expression of genes on Chromosome 21 (“Chr 21”) by targeting an XIST transgene to the Dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) gene or a Regulator of calcineurin 1 (RCAN1) gene, and cells and transgenic animals comprising an XIST transgene inserted into a DYRK1A or RCAN1 allele, e.g., cells and animals trisomic for human Chr 21 and mouse Chr 16.

Abstract: The present invention relates to a human mast cell line corresponding to deposit number CNCM I-4551 and also to the lines derived therefrom, in particular the derived lines corresponding respectively to deposit numbers CNCM I-4552 and CNCM I-4553, and to the uses thereof, in particular for screening for compounds of therapeutic interest.

Abstract: The present invention relates in some aspects to super-enhancers and related compositions, methods, and agents that are useful for modulating expression of cell type-specific genes that are required for maintenance of cell identity (e.g., embryonic stem cell identity) or maintenance of a disease state (e.g., cancer).

Abstract: Methods for increasing specificity of RNA-guided genome editing, e.g., editing using CRISPR/Cas9 systems, using truncated guide RNAs (tru-gRNAs).

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 invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of the HAMP gene (HAMP gene), comprising an antisense strand having a nucleotide sequence which is less that 30 nucleotides in length, generally 19-25 nucleotides in length, and which is substantially complementary to at least a part of the HAMP gene. The invention also relates to a pharmaceutical composition comprising the dsRNA together with a pharmaceutically acceptable carrier; methods for treating diseases caused by HAMP gene expression and the expression of the HAMP gene using the pharmaceutical composition.

Abstract: Some embodiments of this invention include methods for treating disease and methods for administering a compound of the invention. In some aspects of the invention, diseases can be treated by administration of compositions comprising a compound of the invention. Pharmaceutical compositions of some embodiments of the present invention comprise a compound of the invention.

Abstract: Provided are human miRNAs associated with the generation of immunological tolerance during pregnancy as well as fragments, derivatives and variants thereof for use in immunomodulation. Said miRNAs may be used in diagnosis and treatment of disorders associated with a deregulated immune response, autoimmune disorders, pregnancy associated diseases, failure or problems of placentation and complications resulting from allotransplantations. In addition, new pharmaceutical and diagnostic compositions for use in diagnosis and therapy of said disorders are described.

Abstract: The present invention relates to a nucleic acid molecule encoding (I) a polypeptide having the activity of an endonuclease, which is (a) a nucleic acid molecule encoding a polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 1; (b) a nucleic acid molecule comprising or consisting of the nucleotide sequence of SEQ ID NO: 2; (c) a nucleic acid molecule encoding an endonuclease, the amino acid sequence of which is at least 70% identical to the amino acid sequence of SEQ ID NO: 1; (d) a nucleic acid molecule comprising or consisting of a nucleotide sequence which is at least 50% identical to the nucleotide sequence of SEQ ID NO: 2; (e) a nucleic acid molecule which is degenerate with respect to the nucleic acid molecule of (d); or (f) a nucleic acid molecule corresponding to the nucleic acid molecule of any one of (a) to (e) wherein T is replaced by U; (II) a fragment of the polypeptide of (I) having the activity of an endonuclease.

Abstract: Some aspects of this invention provide a non-human animal model of autism. Some aspects of this invention provide a non-human animal model for diseases or disorders associated with an overexpression or a copy number variance of a Ube3a gene. Transgenic mammals and transgenic mammalian cells comprising an exogenous copy or exogenous copies of a ube3a protein-encoding nucleic acid sequence are also provided. Some aspects of this invention further provide methods for using the animal models, cells, and transgenic animals for identifying agents or interventions that can alleviate a pathogenic characteristic observed in the animal model, cell, or transgenic animal.

Abstract: The present invention relates to female germline stem cells and their progenitors, methods of isolation thereof, and methods of use thereof.

Abstract: The present invention concerns methods and compositions involving RNase III and polypeptides containing RNase III domains to generate RNA capable of triggering RNA-mediated interference (RNAi) in a cell. In some embodiments, the RNase III is from a prokaryote. RNase III activity will cleave a double-stranded RNA molecule into short RNA molecules that may trigger or mediate RNAi (siRNA). Compositions of the invention include kits that include an RNase III domain-containing polypeptide. The present invention further concerns methods using polypeptides with RNase III activity for generating RNA molecules that effect RNAi, including the generation of a number of RNA molecules to the same target.

Abstract: The present invention generally relates to methods of making cDNA molecules and cDNA libraries. The invention also relates to cDNA molecules and cDNA libraries produced according to these methods, as well as to vectors and host cells containing such cDNA molecules and libraries. The invention also relates to kits for making the cDNA molecules and libraries of the invention.

Abstract: The invention relates to fluid distribution in an exposure device. The exposure device, in some examples, is a device for exposing living cell cultures or cellular tissues to a fluid such as cigarette smoke, air and/or other gases or gas mixtures, for use in studies of the effects on the cell cultures or tissues of their exposure to the fluid. A fluid distribution member is described for distributing the fluid in the exposure device, the member including a plurality of apertures in a surface arranged such that, when the distribution member is fitted to the fluid exposure device, the distribution member receives fluid applied to the surface of the member and distributes the fluid, via the apertures, to samples to be exposed to the fluid in the exposure device.

Abstract: The present invention features, inter alia, biocompatible compositions that include a poloxamer and one or more additives such as hyaluronic acid, gelatin, fibronectin, or a peptide fragment of fibronectin. The compositions are useful in tissue repair or remodeling, including repair of an injured spinal disc, in drug delivery, in cell culture, and in inhibiting the formation of adhesions.

Abstract: A cell culture comprising human foreskin cells, the human foreskin cells being capable of maintaining stem cells in an undifferentiated state when co-cultured therewith.

Abstract: Creating a tissue structure in vitro includes juxtaposing mandrels on a culture/perfusion device frame where the mandrels are spaced apart substantially parallel to each other and connecting the mandrels to tubes including an upstream tubes and downstream tubes. The upstream tubes are connected with an upstream manifold and the downstream tubes are connected to a downstream manifold. The frame and the mandrels are sterilized, coated and seeded with cells that multiply and form circular layers around each of the mandrels until the circular layers merge into a tissue structure which is subjected to a growth medium. The mandrels are extracted and the tissue structure is perfused.

Abstract: Disclosed are mammalian tau proteases, as well as proteolytically-active fragments, variants, and mutants thereof. Also disclosed are polynucleotides and recombinant expression vectors that encode these polypeptides, as well as methods for producing such proteins in selected recombinant host cells, and for using the compositions in a variety of diagnostic and analytical assays.

Abstract: Disclosed is the three-dimensional (3-D) structure of the GLP-1 receptor (GLP-1R) and methods by which the structure may be used to develop compounds that bind to, and/or modulate the GLP-1R. The technology described herein may be applied to the development of compounds that target the GLP-1R, or may be used to develop target compound that may bind to, and/or modulate the activity of the GLP-1R.

Abstract: The present invention relates to uses of growth and differentiation factor 8 (GDF-8) in vitro or in vivo for reducing the immunogenicity or risk of rejection of cells such as in particular mesenchymal stem cells (MSC), tissues or materials. The present invention further relates to methods for differentiating MSC in vitro or ex vivo into osteoprogenitors or osteoblastic cells or a cell population comprising osteoprogenitors and/or osteoblastic cells using FGF-2 and GDF-8. In addition, the present invention relates to osteoprogenitors or osteoblastic cells or a cell population comprising osteoprogenitors and/or osteoblastic cells obtainable by such methods and to the osteoprogenitors or osteoblastic cells or a cell population comprising osteoprogenitors and/or osteoblastic cells for use in the treatment of musculoskeletal diseases.

Abstract: Methods for generating human endothelial cells from human pluripotent stem cells under defined conditions in the absence of VEGF are described. Wnt/?-catenin signaling is activated in human pluripotent stem cells for a defined period, e.g., by inhibition of Gsk3, and then cultured without further exogenous activation of Wnt/?-catenin signaling to obtain a cell population containing human endothelial cells.

Abstract: Disclosed herein are compositions for linking DNA binding modules to allow for specific and selective binding to module subsites separated by 1 or more base pairs. Also described are methods of making and using compositions comprising these linkers.

Abstract: A method of manipulating the fate of a cell which comprises contacting the cell with at least one of (a) a cell fate-determining untranslated/noncoding RNA species (cuR), (b) a modified cuR, or (c) a compound that modifies or affects cuR, under condition sufficient to cause a cell-changing or cell-maintaining fate that results in cell regeneration, cell differentiation or cell death, so that an increase of desirable cells or a decrease in undesirable cells can be obtained. Another aspect of the invention relates to a method of manipulating the fate of a cell by contacting the cell with a compound that affects a fate-determining mechanism involving homologous nucleic acid interactions of RNA:RNA or RNA:DNA or resolution of such interactions under conditions sufficient to cause a cell-changing or cell-maintaining fate that results in cell regeneration, cell differentiation or cell death, so that an increase of desirable cells or a decrease in undesirable cells can be obtained.

Abstract: The invention provides a peptide comprising a human cytolytic T lymphocyte (CTL) epitope from the human tumor-associated antigen (TAA) New Gene Expressed in Prostate (NGEP), which can be used in vaccine prevention or therapy of prostate cancer, as well as a nucleic acid encoding the peptide, a vector comprising the nucleic acid, a cell comprising the peptide, nucleic acid, or vector, and compositions thereof.

Abstract: Disclosed herein is the finding that Zscan4 is an early embryonic factor that facilitates cellular reprogramming. In particular, Zscan4 can replace the oncogenic reprogramming factor c-Myc to produce induced pluripotent stem cells when co-expressed with Klf4, Oct4 and Sox2. In addition, several Zscan4-dependent genes were identified that promote iPSC formation when co-expressed with known reprogramming factors. Thus, the present disclosure provides an ex vivo method of producing an iPS cell by reprogramming of a somatic cell. The method includes contacting the somatic cell with a Zscan4, or a Zscan4-dependent gene, and at least one reprogramming factor. Also provided are iPS cells produced by the disclosed method and non-human animals generated from such iPS cells.

Abstract: This invention relates to methods and compositions for use improving cell viability, particularly neural cell viability, and more particularly to methods and compositions for use improving cell viability by reducing reactive oxygen metabolite-mediated oxidative damage in a cell, regulating redox homeostasis in a cell, or reducing mitochondrial dysfunction in a cell. The invention further relates to the administration of the bile acid tauroursodeoxycholic acid (TUDCA) in combination with phenylbutyric Acid (PBA) to improve cell viability, and treat at least one symptom associated with, prevent the time of onset of, or slow the development of a disease related to oxidative stress.

Abstract: The present invention relates to methods of producing chondrocytes, improving the phenotype of a chondrocyte population, promoting chondrogenesis, maintaining a cell population in a differentiated state or increasing the number of cells of a population in a differentiated state, producing a population of differentiated cells, and treating certain diseases or disorders.

Abstract: The present invention relates to methods of inducing differentiation of stem cells. In particular, the invention relates to methods of inducing differentiation of embryonic stem cells into muscle cells or vascular endothelial cells. The invention also includes cells, cell lines, testing models and culture systems used in the methods of the present invention and differentiated cells produced therefrom. The present invention also provides methods of using the differentiated cells of the present invention for therapeutic purposes.

Abstract: A blood coagulation factor VII derivative, a blood coagulation factor VIIa derivative, FacVII and FacVIIa conjugates are prepared by linking a polymer capable of extending the blood half-life to the derivative. FacVII and VIIa complexes each prepared by linking a carrier to the conjugate, genes encoding the FacVII and FacVIIa derivatives, expression vectors comprising the genes, transformants introduced with the expression vectors, a method for preparing the FacVII and FacVIIa derivatives using the transformants, a method for preparing the FacVIIa conjugate and complex, a FacVIIa complex prepared by the method, a pharmaceutical composition for the prevention or treatment of hemophilia comprising the derivative, conjugate, or complex as an active ingredient, and a pharmaceutical composition for blood coagulation comprising the derivative, conjugate, or complex as an active ingredient are described.

Abstract: There are disclosed TIMP-3 muteins, variants and derivatives, nucleic acids encoding them, and methods of making and using them.

Abstract: Disclosed herein are methods and compositions for inactivating a FUT8 gene, using fusion proteins comprising a zinc finger protein and a cleavage domain or cleavage half-domain. Polynucleotides encoding said fusion proteins are also provided, as are cells comprising said polynucleotides and fusion proteins.

Abstract: Disclosed are immunogens including a recombinant RSV F protein stabilized in a prefusion conformation. Also disclosed are nucleic acids encoding the immunogens and methods of producing the immunogens. Methods for generating an immune response in a subject are also disclosed. In some embodiments, the method is a method for treating or preventing a RSV infection in a subject by administering a therapeutically effective amount of the immunogen to the subject.

Abstract: The present invention relates to methods of constructing an integrated artificial immune system that comprises appropriate in vitro cellular and tissue constructs or their equivalents to mimic the normal tissues that interact with vaccines in mammals. The artificial immune system can be used to test the efficacy of vaccine candidates in vitro and thus, is useful to accelerate vaccine development and testing drug and chemical interaction with the immune system.