Abstract: Provided are novel methods and compositions for the modulation of thermogenesis. Such methods are particularly advantageous in that they allow for the reduction of body fat in a subject without the subject having to adjust their caloric intake through dieting, modify their physical activity or undergo bariatric surgery. Accordingly, the methods of the invention are particularly useful for treating or preventing obesity. Also provided are methods of screening for novel agents that modulate the activity of thermogenic regulators.

Abstract: An object of the present invention is to provide methods for producing iPS cells with low invasivity and high efficiency. The iPS cells can be produced with high efficiency using a method comprising the steps of culturing mononuclear cells derived from peripheral blood for 3 to 14 days in the presence of anti-CD3 antibody, and subjecting the cultured mononuclear cells to dedifferentiation.

Abstract: The present invention is concerned with a method and a kit for detecting an interaction between a first membrane bound test protein or fragment thereof and a second test protein or fragment thereof which is either membrane bound or soluble with an in vivo genetic system based in yeast, bacterial or mammalian cells. The system makes use of the reconstitution of the split ubiquitin protein.

Abstract: Method and kit for constructing a random mutagenesis library. The method comprises providing a first expression vector comprising a target polynucleotide fragment, providing a pair of Vector-primers that are complementary to the vector portion of the first expression vector, wherein the Vector-primers comprise a second selection marker gene, and wherein the Vector-primers allow PCR amplification of the target polynucleotide; and performing a PCR reaction using the first expression vector as the template with the Vector-primers under error-prone PCR conditions in the presence of a thermostable DNA ligase, generating a second expression vector which comprises the second selection marker gene and a mutated target polynucleotide.

Abstract: Provided is a method of producing an iPS cell, comprising bringing (a) Oct3/4 or a nucleic acid that encodes the same, (b) Klf4 or a nucleic acid that encodes the same, and (c) Sox2 or a nucleic acid that encodes the same, as well as (d1) L-Myc or a nucleic acid that encodes the same and/or (d2) a functional inhibitor of p53, into contact with a somatic cell. It is preferable that (a) a nucleic acid that encodes Oct3/4, (b) a nucleic acid that encodes Klf4, (c) a nucleic acid that encodes Sox2, (d1) a nucleic acid that encodes L-Myc and (e) a nucleic acid that encodes Lin28 or Lin28b be inserted into an episomal vector having loxP sequences placed in the same orientation on the 5? and 3? sides of a vector constituent essential for the replication of the vector, that (d2) a nucleic acid that encodes an shRNA against p53 be inserted into a vector ensuring transient expression (plasmid vector and the like), and that all these nucleic acids be transferred to a somatic cell.

Abstract: Methods and means are provided for reducing the phenotypic expression of a nucleic acid of interest in eukaryotic cells, particularly in plant cells, by providing aberrant, preferably unpolyadenylated, target-specific RNA to the nucleus of the host cell. Preferably, the unpolyadenylated target-specific RNA is provided by transcription of a chimeric gene comprising a promoter, a DNA region encoding the target-specific RNA, a self-splicing ribozyme and a DNA region involved in 3? end formation and polyadenylation.

Abstract: The present invention features methods for stimulating clearance of misfolded or aggregated proteins or peptides in microglia or neurons, and treating neurodegenerative diseases associated with such pathology in brain by selectively inhibiting the expression or activity of Acyl-CoA:Cholesterol Acyltransferase 1, but not Acyl-CoA:Cholesterol Acyltransferase 2.

Abstract: The present invention features methods for stimulating clearance of misfolded or aggregated proteins or peptides in microglia, and treating neurodegenerative diseases associated with such pathology in brain by selectively inhibiting the expression or activity of Acyl-CoA:Cholesterol Acyltransferase 1, but not Acyl-CoA:Cholesterol Acyltransferase 2.

Abstract: The present invention is related to a method of classifying a sample of a patient who suffers from or being at risk of developing cancer, said method comprising the steps of determining in said sample from said patient, on a non protein basis, the expression level of at least one gene encoding for a hormone receptor selected from the group comprising estrogen receptor, progesterone receptor and/or androgen receptor in said sample; comparing the one or more expression level(s) determined with one or more expression level(s) of one or more reference genes, and classifying the sample of said patient from the outcome of the comparison into one of at least two classifications.

Abstract: Disclosed are compositions and methods related to the interaction of polyCUG and polyCCUG repeat RNA and proteins that bind to these repetitive RNA sequences. Also disclosed are methods of treating DM1 or DM2 comprising inhibiting the interaction of poly(CUG)exp or poly(CCUG)exp RNA with muscleblind proteins, or by causing improvement of spliceopathy in myotonic dystrophy.

Abstract: Processes, vectors and engineered cell lines for large-scale transfection and protein production in mammalian cells, especially Chinese Hamster Ovary (CHO) cells are described in which transfection efficiencies are realized through the use of a single vector system, the use of functional oriP sequences in all plasmids, the use of codon-optimized Epstein-Barr virus nuclear antigen-1 (EBNA1) constructs, the use of a fusion protein between a truncated Epstein-Barr virus nuclear antigen-1c (EBNA1c) protein and a herpes simplex virus protein VP16, the use of a 40 kDa fully deacetylated poly(ethylenimine) as a transfection reagent, the use of co-expression of a fibroblast growth factor (FGF) and/or the use of protein kinase B to potentiate heterologous gene expression enhancement by valproic acid (VPA).

Abstract: Coronatine has been found to enhance binding of the JAZ1 degron to the Arabidopsis F-box protein COI1, and analysis of the JAZ1 degron sequence has resulted in the identification of specific peptide sequences that bind COI1 with high affinity in the presence of coronatine. Crystal structure analysis has determined that coronatine and JA-Ile enhance the interaction between COI1 and JAZ1 via binding to a specific binding pocket on COI1. Attachment of one or more JAZ1 peptide tags as disclosed herein to a target protein in a non-plant cell expressing Arabidopsis COI1 or a homolog thereof results in degradation of the target protein following addition of a molecule that binds the coronatine/JA-Ile binding pocket on COI1. Therefore, provided herein are compositions, methods, and kits for targeted protein degradation.

Abstract: The present disclosure provides a method of modifying cells in order to enhance lentiviral titers, cell lines that are modified and modifying reagents. By mediating individual genes and combination thereof, lentiviral titers may be increased.

Abstract: Provided herein are compositions for reducing CLPTM1L expression in a cell as well as methods for using such compositions to treat or prevent cancer in a subject. In particular, compositions comprising RNAi-inducing constructs targeted to CLPTM1L and methods of administering such compositions to a subject to treat or prevent a disease or condition associated with CLPTM1L over-expression (e.g., lung cancer) are provided herein.

Abstract: Disclosed are compounds, compositions and methods for systemic and local delivery of biologically active molecules.

Abstract: A gene construct comprising a programmed-cell-death executioner gene having a nuclear localization signal, a deleted signal peptide, an inhibitor-resistant binding site, a promoter, and an activator. A method of making a gene construct, by modifying a programmed-cell-death executioner gene by adding a nuclear localization signal, deleting a signal peptide, mutating a binding site for an inhibitor to make it inhibitor-resistant, adding a promoter for exclusive expression in selected cells, and adding an activator. A method of eliminating undesired cells from a patient. A method of treating cancer. An array comprising at least two gene constructs wherein all of the gene constructs differ with respect to the programmed-cell-death executioner gene and the nuclear localization signal. A method of personalizing anti-cancer treatment. A method of increasing DNase 1 resistance to actin binding. A method of increasing catalytic activity of DNase 1 binding.

Abstract: Disclosed herein are recombinant human progenitor cells, engineered human thymocytes, and engineered human T cells. The recombinant human progenitor cells are made by transducing a human hematopoietic stem cell with a vector having a nucleic acid molecule which encodes a human T cell receptor specific to a virus, such as Human Immunodeficiency Virus, or an epitope thereof. The recombinant human progenitor cells differentiate and mature into the engineered human thymocytes and the engineered human T cells. Also disclosed herein are methods of inhibiting, reducing or treating a viral infection in a subject, such as a human subject, which comprises administering recombinant human progenitor cells, engineered human thymocytes, and/or engineered human T cells to the subject.

Abstract: The present invention relates to a method for treating a cancer including a combination of a treatment by a nucleic acid molecule mimicking double strand breaks with hyperthermia.

Abstract: Compositions and methods are provided for depletion of pluripotent cells. In one embodiment of the invention, methods are provided for depletion of pluripotent cells from a mixed population of differentiated cells and stem cells, to provide a population of cells substantially free of pluripotent stem cells. Monoclonal antibodies useful in depletion and in identification of pluripotent stem cells are also provided.

Abstract: The embodiments disclosed herein relate to the construction of fully-deleted Adenovirus-based gene delivery vectors packaged without helper Adenovirus, and more particularly to their use in gene therapy for gene and protein expression, vaccine development, and immunosuppressive therapy for allogeneic transplantation. In an embodiment, a method for propagating an adenoviral vector includes (a) providing an Adenovirus packaging cell line; (b) transfecting a fully-deleted Adenoviral vector construct into the cell line; and optionally (c) transfecting a packaging construct into the cell line, wherein the fully-deleted Adenoviral vector construct and optionally the packaging construct can transfect the Adenovirus packaging cell line resulting in the encapsidation of a fully-deleted Adenoviral vector independent of helper Adenovirus. In an embodiment, a target cell is transduced with the encapsidated fully-deleted Adenoviral vector for treating a condition, disease or a disorder.

Abstract: The presently disclosed subject matter provides populations of stem cells that are purified from bone marrow, peripheral blood, and/or other sources. Also provided are methods of using the stem cells for treating tissue and/or organ damage in a subject.

Abstract: There are provided Idbf (inhibitor of Dvl and bone formation) which is a novel Dvl-binding protein that binds to Dvl to inhibit signal transduction carried out through the Wnt/?-catenin signaling pathway, a gene for coding for the same, the use thereof, and the use of an inhibitor of the Idbf. The Idbf was known to be expressed by activation of the Wnt/?-catenin signaling pathway and bind to Dvl to block signal transduction carried out through the Wnt/?-catenin signaling pathway. Therefore, the Idbf can be used in development of medicines for inhibiting the signal transduction carried out through the Wnt/?-catenin signaling pathway, and an Idbf inhibitor can be used in preparation of medicines for activating the signal transduction carried out through the Wnt/?-catenin signaling pathway.

Abstract: Oogonial stem cell (OSC)-derived compositions, such as nuclear free cytoplasm or isolated mitochondria, and uses of OSC-derived compositions in autologous fertility-enhancing procedures are described.

Abstract: Compositions and methods for inducing the formation of an induced pluripotential stem (iPS) cell from a somatic cell are disclosed. The compositions comprise miR 302-367 cluster and valproic acid. Further disclosed are methods for treatment of a disease or condition in a subject through the use of the compositions.

Abstract: The invention relates to oligonucleotide-oligocation molecules AiBjH that can be synthetized via automated phosphoramidite chemistry having oligonucleotides moieties Ai and oligocations moieties Bj, wherein •Ai is an i-mer oligonucleotide residue, with i=5 to 50, where nucleotide A is an oligomer with naturally or non naturally occurring nucleobases and/or pentafuranosyl groups and/or native phosphodiester bonds, for example selected from the group comprising deoxyribo, ribo, locked (LNA) nucleotides as well as their chemical modifications or substitutions such as phosphorothioate, 2?-fluoro, 2?-O-alkyl, or a marker group such as a fluorescent agent, •Bj is a j-mer organic oligocation moiety, with j=1 to 50, where B is selected from the group comprising •—HPO3—R1—(X—R2n)n1—X—R3—O—, where R1, R2n and R3, identical or different, are lower alkylene, X is NH or NC(NH2)2, n varies from 1 to 5 and n1=2 to 20, •—HPO3—R4—CH(R5X1)—R6—O—, where R4 is lower alkylene, R5 and R6, identical or different, are lower alkylene

Abstract: Methods of making mutant Cas9 proteins are described.

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: There is provided an expression vector for animal cell having an increased gene expression efficiency, and particularly, an expression vector for animal cells including a MAR element and a SAR element, which are gene expression increasing factors, at a 5? end of a promoter, a 3? end of a transcription termination site, or at both of the 5? end of the promoter and the 3? end of the transcription termination site. The expression vector for animal cells according to the present invention exhibits remarkably increased gene expression efficiency as compared to conventional expression vectors for animal cells, such that protein expression of foreign genes may be significantly increased using this expression vector for animal cells. Particularly, the expression vector for animal cells according to the present invention may be useful in that a high-expression cell line may be secured even without MTX amplification.

Abstract: The present invention concerns the use of methods for evaluating ?-adrenergic receptor targeting agent treatment for a patient, particularly one with a heart condition. In general, the disclosed methods entail determining the presence or absence of one or more polymorphisms in an endothelin gene system member. Based on the results of this determination, a ?-adrenergic receptor targeting agent may be prescribed, administered or a treatment regimen altered, including the administration of a ?-blocker. Accordingly, methods of treatment are also described.

Abstract: The invention relates to the rational mutagenesis of polypeptides of ?/? T-cell receptors that mediate an oncogen-specific T-cell response, nucleic acids encoding these and their use in the therapy, diagnosis and/or prevention of cancerous diseases. The invention further relates to a T-cell response-mediating MDM2-protein-specific ?/? T-cell receptor, which has been rationally mutated by means of the method according to the present invention, and the uses thereof.

Abstract: This invention relates to the inhibition of a newly discovered growth-stimulating protein in an individual. Further, the invention relates to a method for preventing or treating a cancer, or preventing or treating cancer growth, invasion or metastasis, or preventing or treating other hyperproliferative diseases in an individual, by down regulating the expression of said growth-stimulating protein or by inactivating said protein. Still further, the invention concerns a method for diagnosing cancer or other hyperproliferative diseases in an individual based on said growth-stimulating protein.

Abstract: The present invention relates to a viral particle. The viral particle has a radius of less than about 1 ?m, and at least one peptide comprising at least a biologically active portion of CD47. The present invention also includes a method of increasing the life of a particle in vivo in a mammal. The method includes the steps of expressing at least one peptide comprising at least a biologically active portion of CD47 in a viral particle, and administering the viral particle having CD47 expressed to a mammal, wherein the administered viral particle has a longer half life in the mammal than an otherwise identical viral particle that does not have CD47 expressed thereon.

Abstract: The present invention provides three-dimensional microenvironment niches prepared from biomaterial compositions that supports growth and self renewal of stem cells. The invention also provides methods for inducing pluripotency in a somatic cell using chemical compounds, as well as methods for screening for compounds that can induce pluripotency in a somatic cell.

Abstract: The invention relates to DNA-sequences, especially transcription- or expression-enhancing elements (TE elements) and their use on an expression vector in conjunction with an enhancer, a promoter, a product gene and a selectable marker. TE elements bring about an increase in the expression of the product gene, particularly when stably integrated in the eukaryotic genome, preferably the CHO-DG44 genome.

Abstract: Disclosed herein are methods and materials for producing a more developmentally potent cell from a less developmentally potent cell. Specifically exemplified herein are methods that comprise introducing an expressible dedifferentiating polynucleotide sequence into a less developmentally potent cell, wherein the transfected less developmentally potent cell becomes a more developmentally potent cell capable of differentiating to a less developmentally potent cell of its lineage of origin or a different lineage.

Abstract: The present invention provides; a novel gene introduction method which enables a gene to be introduced more safely and more freely, particularly a method for introducing a gene into a specified site in the brain safely and freely; a carrier for gene introduction use, which comprises a nano-particle and a substance capable of binding to a vector for gene introduction and has functional groups involved in the induction of phagocytosis by cells, wherein the substance capable of binding to a vector for gene introduction can bind to the surface of the nano-particle through some of the functional groups and another some of the functional groups remain unbound to the substance capable of binding to a vector for gene introduction; and a gene introduction agent, in which a vector for gene introduction is bound to the substance capable of binding to a vector for gene introduction in the carrier for gene introduction.

Abstract: This disclosure is directed to methods for reproducibly generating substantial amounts of endothelial cells from amniotic cells. The endothelial cells generated in accordance with the present methodology, as well as therapeutic methods utilizing these cells, are also disclosed.

Abstract: The invention concerns a system for modulating tissue physiology, for example, to prevent or reverse tissue damage caused by disease. The system utilizes vigilant cells that include stable vectors containing a gene switch/biosensor and a gene amplification system. The vectors allow expression of a transgene (such as a cardioprotective gene) in the vigilant cells to be regulated in response to a physiological signal, to be switched on or off, and to provide sufficient levels of the transgene product to achieve a desired result, e.g., prevention or reversal of myocardial cell damage. In addition to myocardial infarction, the vectors can be used to treat cells in a number of other disease states, including diabetes, cancer, stroke, and atherosclerosis. These approaches to stem cell-based gene therapy provide a novel strategy not only for treatment but for prevention of cell destruction.

Abstract: Disclosed herein are chimeric receptors comprising an extracellular domain with affinity and specific for the Fc portion of an immunoglobulin molecule (Ig) (e.g., an extracellular ligand-binding domain of F158 FCGR3A or V158 FCGR3A variant); a transmembrane domain (e.g., a transmembrane domain of CD8?); at least one co-stimulatory signaling domain (e.g., a co-stimulatory signaling domain of 4-1BB); and a cytoplasmic signaling domain comprising an immunoreceptor tyrosine-based activation motif (ITAM) (e.g., a cytoplasmic signaling domain of CD3?). Also provided herein are nucleic acids encoding such chimeric receptors and immune cells expressing the chimeric receptors. Such immune cells can be used to enhance antibody-dependent cell-mediated cytotoxicity and/or to enhance antibody-based immunotherapy, such as cancer immunotherapy.

Abstract: The present invention is based on the seminal discovery that cord blood (CB) and adult bone marrow (BM) CD34+ cells can be reprogrammed to early stem cells. The invention provides the reprogramming of CB and adult bone marrow (BM) CD34+ cells from subjects without any pre-treatment. Provided are methods for reprogramming blood cells of a subject. Also provided are methods of disease modeling and methods of generating subject-specific differentiated cells. In addition, the invention provides methods of identifying an agent that alters a function of subject-specific differentiated cells as well as isolated pluripotent or multipotent stem cells reprogrammed from blood cells.

Abstract: Provided is a method of producing an iPS cell, comprising bringing (a) Oct3/4 or a nucleic acid that encodes the same, (b) Klf4 or a nucleic acid that encodes the same, and (c) Sox2 or a nucleic acid that encodes the same, as well as (d1) L-Myc or a nucleic acid that encodes the same and/or (d2) a functional inhibitor of p53, into contact with a somatic cell. It is preferable that (a) a nucleic acid that encodes Oct3/4, (b) a nucleic acid that encodes Klf4, (c) a nucleic acid that encodes Sox2, (d1) a nucleic acid that encodes L-Myc and (e) a nucleic acid that encodes Lin28 or Lin28b be inserted into an episomal vector having loxP sequences placed in the same orientation on the 5? and 3? sides of a vector constituent essential for the replication of the vector, that (d2) a nucleic acid that encodes an shRNA against p53 be inserted into a vector ensuring transient expression (plasmid vector and the like), and that all these nucleic acids be transferred to a somatic cell.

Abstract: The method for producing a pancreatic hormone-producing cell according to the present invention is characterized in that a specific differentiation/induction promoter is added to a culture medium in the process of differentiating/inducing of a pluripotent stem cell or a pancreatic tissue stem/progenitor cell into the pancreatic hormone-producing cell. The differentiation/induction promoter to be used is: a polypeptide which comprises an amino acid sequence encoded by DNA comprising the nucleotide sequence represented by SEQ ID NO: 1 or a variant thereof; or a culture supernatant of a cell into which DNA comprising the nucleotide sequence represented by SEQ ID NO: 1 or DNA capable of hybridizing with DNA comprising a nucleotide sequence complementary to the aforementioned DNA under stringent conditions is integrated as a foreign gene.

Abstract: The present invention relates to a therapeutic polypeptide and methods for its creation and use for modulating an immune response in a host organism in need thereof. In particular, the invention relates to the administration to an organism in need thereof, of an effective amount of a pre-coupled polypeptide complex comprising a lymphokine polypeptide portion, for example IL-15 (SEQ ID NO: 5, 6), IL-2 (SEQ ID NO: 10, 12) or combinations of both, and an interleukin receptor polypeptide portion, for example IL-15Ra (SEQ ID NO: 7, 8), IL-2Ra (SEQ ID NO: 9, 11) or combinations of both, for augmenting the immune system in, for example, cancer, SCID, AIDS, or vaccination; or inhibiting the immune system in, for example, rheumatoid arthritis, or Lupus. The therapeutic complex of the invention surprisingly demonstrates increased half-life, and efficacy in vivo.

Abstract: This invention relates to a method for producing a protein of interest, comprising introducing a protein expression vector which comprises a gene fragment a gene fragment comprising a DNA encoding a protein of interest and a selectable marker gene and transposon sequences at both terminals of the gene fragment, into a suspension mammalian cell; integrating the gene fragment inserted between a pair of the transposon sequences, into a chromosome of the mammalian cell to obtain a mammalian cell capable of expressing the protein of interest; and suspension-culturing the mammalian cell; and a suspension mammalian cell capable of expressing the protein of interest.

Abstract: This disclosure provides methods and compositions for treating disorders or injuries that affect motor function and control in a subject. In one aspect, the invention a transgene product is delivered to a subject's spinal cord by administering a recombinant neurotrophic viral vector containing the transgene to the brain. The viral vector delivers the transgene to a region of the brain which is susceptible to infection by the virus and which expresses the encoded recombinant viral gene product. Also provided are compositions for delivery of a transgene product to a subject's spinal cord by administering a recombinant neurotrophic viral vector containing the transgene to the subject's brain.

Abstract: In one aspect, the invention provides methods and compositions for the expression of small RNA molecules within a cell using a retroviral vector (FIG. 1A). Small interfering RNA (siRNA) can be expressed using the methods of the invention within a cell. In a further aspect, the invention provides methods for producing siRNA encoding lentivirus where the siRNA activity may interfere with the lentiviral life cycle. In yet a further aspect, the invention provides methods for expression of a small RNA molecule within a cell, such as an siRNA capable of downregulating CCR5, wherein expression of the small RNA molecule is relatively non-cytotoxic to the cell. The invention also includes small RNA molecules, such as an siRNA capable of downregulating CCR5, that are relatively non-cytotoxic to cells.

Abstract: The present invention provides a method of expressing at least one heterologous nucleic acid sequence in a cell, the method comprising introducing at least one heterologous nucleic acid sequence into a cell by infecting said cell with a recombinant negative-strand RNA virus vector comprising said at least one heterologous nucleic acid sequence, wherein the recombinant negative-strand RNA virus vector includes a viral genome coding for a mutated P protein, which leads to a loss of the viral genome replication ability without a loss of the viral transcription ability, and wherein said at least one heterologous nucleic acid sequence encodes a cellular reprogramming or programming factor or a therapeutic protein. In addition, the present invention provides a cell or a population of cells prepared in vitro by said method as well as a pharmaceutical composition comprising said cell or population of cells.

Abstract: The present disclosure is in the field of genome engineering, particularly targeted modification of the genome of a hematopoietic cell.

Abstract: Methods for de-differentiating or altering the life-span of desired “recipient” cells, e.g., human somatic cells, by the introduction of cytoplasm from a more primitive, less differentiated cell type, e.g., oocyte or blastomere are provided. These methods can be used to produce embryonic stem cells and to increase the efficiency of gene therapy by allowing for desired cells to be subjected to multiple genetic modifications without becoming senescent. Such cytoplasm may be fractionated and/or subjected to subtractive hybridization and the active materials (sufficient for de-differentiation) identified and produced by recombinant methods.

Abstract: The subject invention provides materials and method for making a recessive gene dominant. This is accomplished by interfering with the natural mechanisms that inhibit expression of the recessive gene and/or by interfering with the expression of the naturally dominant gene. In a preferred embodiment, the method of the subject invention comprises both reducing inhibition of expression of the recessive gene and increasing inhibition of the dominant gene.