Abstract: In some embodiments, an antiviral vector is provided. The antiviral vector includes a replication competent adeno-associated virus (AAV) and an inhibitory expression cassette that includes a nucleotide sequence that encodes an RNAi molecule that inhibits expression of a targeted helper virus (THV) gene. The THV gene may be part of an Adenovirus (Ad) genome, a Human Papillomavirus (HPV) genome, a Human Herpes Virus (HHV) genome, or a Vaccinia virus (W) genome.

Abstract: Isolated polynucleotides comprising a FEV mini-promoters are provided. The mini-promoter may be operably linked to an expressible sequence, e.g. reporter genes, genes encoding a polypeptide of interest, regulatory RNA sequences such as miRNA, siRNA, anti-sense RNA, etc., and the like. In some embodiments a cell comprising a stable integrant of an expression vector is provided, which may be integrated in the genome of the cell. The promoter may also be provided in a vector, for example in combination with an expressible sequence. The polynucleotides find use in a method of expressing a sequence of interest, e.g. for identifying or labeling cells, monitoring or tracking the expression of cells, gene therapy, etc.

Abstract: The present invention provides isolated epitope peptides derived from TOPK and immunogenic fragments thereof have an ability to induce cytotoxic T lymphocytes (CTLs) and thus are suitable for use in cancer immunotherapy, more particularly as cancer vaccines. The peptides of the present invention encompass both of peptides including a TOPK-derived amino acid sequence and modified versions thereof, in which one, two, or several amino acids are substituted, deleted, inserted and/or added, provided such modified versions have CTL inducibility. Further provided are polynucleotides encoding any of the aforementioned peptides as well as pharmaceutical compositions that include any of the aforementioned peptides or polynucleotides. The peptides, polynucleotides, and pharmaceutical compositions of this invention find particular utility in either or both of the treatment and prevention of a number of cancers.

Abstract: Disclosed are materials and methods for treating diseases of the mammalian eye, and in particular, Usher syndrome 1B (USH1B). The invention provides AAV-based, dual-vector systems that facilitate the expression of full-length proteins whose coding sequences exceed that of the polynucleotide packaging capacity of an individual AAV vector. In one embodiment, vector systems are provided that include i) a first AAV vector polynucleotide that includes an inverted terminal repeat at each end of the polynucleotide and a suitable promoter followed by a partial coding sequence that encodes an N-terminal portion of a full-length polypeptide; and ii) a second AAV vector polynucleotide that includes an inverted terminal repeat at each end of the polynucleotide and a partial coding sequence that encodes a C-terminal portion of a full-length polypeptide, optionally followed by a polyadenylation (pA) signal sequence.

Abstract: The present invention relates to a recombinant host cell, wherein the cell is modified to increase the expression levels of Ero1 and XBP1 relative to the expression levels of Ero1 and XBP1 in an unmodified cell. The present invention also relates to a method of producing a recombinant protein of interest comprising expressing the recombinant protein of interest in the recombinant host cell.

Abstract: Circular nucleic acid vectors that provide for persistently high levels of protein expression are provided. The circular vectors of the subject invention are characterized by being devoid of expression-silencing bacterial sequences, where in many embodiments the subject vectors include a unidirectional site-specific recombination product hybrid sequence in addition to an expression cassette. Also provided are methods of using the subject vectors for introduction of a nucleic acid, e.g., an expression cassette, into a target cell, as well as preparations for use in practicing such methods. The subject methods and compositions find use in a variety of different applications, including both research and therapeutic applications. Also provided is a highly efficient and readily scalable method for producing the vectors employed in the subject methods, as well as reagents and kits/systems for practicing the same.

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: Improved poly(amido ethylenimine) copolymers for gene delivery are disclosed. One illustrative embodiment includes polyethylene glycol (PEG) covalently bonded to a branched poly(triethyenetetramine/cystamine bisacrylamide) copolymer (poly(TETA/CBA)). The polyethylene glycol can be linear or branched. Another illustrative embodiment includes an RGD peptide covalently bonded to the poly(TETA/CBA)-PEG conjugate. Still another illustrative embodiment includes a method of using these compositions for transfecting a cell with a nucleic acid.

Abstract: The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotides, primary transcripts and mmRNA molecules.

Abstract: The present invention provides peptides having an amino acid sequence as set forth in SEQ ID NO: 19, 22, 30, 34, 344, 358, 41, 44, 46, 48, 78, 376, 379, 80, 100, 101, 110, 111, 387, 112, 394, 114, 116, 117, 121, 395, 133, 135, 137, 426, 143, 147, 148, 149, 150, 152, 153, 154, 156, 160, 161, 162, 163, 166, 174, 178, 186, 194, 196, 202, 210, 213, 214, 217, 223, 227, 228, 233, 254, 271, 272 or 288, as well as peptides having the above-mentioned amino acid sequences in which 1, 2, or several (e.g., up to 5) amino acids are substituted, deleted, or added, provided the peptides possess cytotoxic T cell inducibility. The present invention also provides drugs for treating or preventing a disease associated with over-expression of the CDH3, EPHA4, ECT2, HIG2, INHBB, KIF20A, KNTC2, TTK and/or URLC10, e.g. cancers containing as an active ingredient one or more of these peptides. The peptides of the present invention find further utility as vaccines.

Abstract: Isolated polynucleotides comprising a DCX mini-promoters are provided. The mini-promoter may be operably linked to an expressible sequence, e.g. reporter genes, genes encoding a polypeptide of interest, regulatory RNA sequences such as miRNA, siRNA, anti-sense RNA, etc., and the like. In some embodiments a cell comprising a stable integrant of an expression vector is provided, which may be integrated in the genome of the cell. The promoter may also be provided in a vector, for example in combination with an expressible sequence. The polynucleotides find use in a method of expressing a sequence of interest, e.g. for identifying or labeling cells, monitoring or tracking the expression of cells, gene therapy, etc.

Abstract: This invention provides the use of AChE as nuclease. The use of AChE in regulating the stability of nucleic acid and cell apoptosis, as well as a series of agents based on the use, including the agents for promoting or inhibiting cell apoptosis, the agents for inhibiting tumors, and the agents for protecting nucleic acid from impairing, are provided.

Abstract: The invention concerns the field of recombinant gene engineering. It concerns novel introns and compositions comprising such introns as well as a method to improve expression of polypeptides from nucleic acids such as cloned genes with heterologous introns, especially genes encoding antibodies and antibody derived fragments, and the production of various polypeptides in eukaryotic host cells using said novel intron sequences as heterologous introns.

Abstract: Provided are isolated genomic polynucleotide fragments that encode human SNARE YKT6, human glucokinase, human adipocyte enhancer binding protein (AEBP1) and DNA directed 50 kD regulatory subunit (POLD2), vectors and hosts containing these fragments and fragments hybridizing to noncoding regions as well as antisense oligonucleotides to these fragments. The invention is further directed to methods of using these fragments to obtain SNARE YKT6, human glucokinase, AEBP1 protein and POLD2 and to diagnose, treat, prevent and/or ameliorate a pathological disorder.

Abstract: This invention provides methods to prepare and use immunostimulatory cells for enhancing an immune response. The invention provides a method for preparing mature dendritic cells (DCs), comprising the sequential steps of: (a) signaling isolated immature dendritic cells (iDCs) with a first signal comprising an interferon gamma receptor (IFN-?R) agonist and/or a tumor necrosis factor alpha receptor (TNF-?R) agonist to produce signaled dendritic cells; and (b) signaling said signaled dendritic cells with a second transient signal comprising an effective amount of a CD40 agonist to produce CCR7+ mature dendritic cells. Also provided by this invention are enriched populations of dendritic cells prepared by the methods of the invention. Such dendritic cells have enhanced immunostimulatory properties and increased IL-12 secretion and/or decreased IL-10 secretion. CD40 signaling can be initiated by one or more of polypeptide translated from an exogenous polynucleotide encoding CD40L (e.g.

Abstract: There are provided a DNA construct comprising a suppressor tRNA gene of a non-eukaryote containing no internal promoter functioning in a eukaryotic cell, and a eukaryotic or bacteriophage promoter linked at the 5? end of the tRNA gene, a method for synthesizing a suppressor tRNA by using the DNA construct, and a process for producing protein incorporating a non-natural amino acid by using the same.

Abstract: Disclosed herein are methods and compositions for targeted integration of an exogenous sequence into the human PPP1R12C locus, for example, for expression of a polypeptide of interest.

Abstract: Methods and products for the repair of genetically defective DNA in the region of a mutated exon, for the specific destruction of tumor cells, and for the identification of naturally trans-spliced RNA. The methods inter alia are based on the utilization of cellular RNA splicing components.

Abstract: Compositions and methods for targeted delivery of therapeutic agents, and particularly for mucosal, oral, nasal, or parenteral delivery of therapeutic agents. The compositions comprise carrier particles containing or encapsulating a therapeutic agent or agents, which have been modified on their surface to contain one or more targeting moieties that enable the enhanced uptake and transport of the therapeutic agent via receptor-mediated processes such as endocytosis or transcytosis.

Abstract: Provided are compositions and methods for delivering biological moieties such as modified nucleic acids into cells to modulate protein expression. Such compositions and methods include the use of modified messenger RNAs, and are useful to treat or prevent diseases, disorders or conditions, or to improve a subject's heath or wellbeing.

Abstract: Methods and compositions for increasing nuclease-mediated genomic modification using DNA repair inhibitors are provided.

Abstract: The invention is directed to methods for generating pancreatic progenitor cells, insulin producing cells or endoderm cells using embryonic stem cells and induced pluripotent stem cells.

Abstract: Disclosed are methods of treating a muscle disease and improving normal muscle function by administering a therapeutically effective amount of an isoprenoid antibiotic. Also disclosed are methods of upregulating hnRNP L and hnRNP L targets by administering a therapeutically effective amount of an isoprenoid antibiotic. Methods of screening compounds for use in treating muscle disease and improving muscle function are also described.

Abstract: Compounds and compositions for the transient expression of exogenous telomerase activity in a cell are provided. The compounds and compositions, which relate to a ribonucleic acid coding for a telomerase reverse transcriptase, are useful in the extension of telomeres in cells needing such treatment. Such cells include, for example, cells that contain shortened telomeres and cells from subjects that may benefit from telomere extension, for example subjects that suffer from, or are at risk of suffering from, age-related or other illnesses. Also provided are methods of extending telomeres through the administration of the provided compounds and compositions to animal cells, either in vitro or in vivo, and kits including the compounds or compositions and instructions for use.

Abstract: A transformed T-cell for T-cell therapy, and a composition including the same for anticancer immunotherapy. More particularly, the transformed T-cell is characterized by the transfection of a gene for coding a chimera protein. The T-cell, to which the gene for coding the chimera protein is transected, may improve the therapeutic effects induced by immune tolerance of cancer cells, and furthermore maximize anti-cancer effects by activating signal transduction to induce the activation of T-cells. Also, the disclosure allows treatments that minimize side effects such as the development of autoimmune diseases due to systematic T-cell activation.

Abstract: The invention provides for engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are compositions and methods related to components of a CRISPR complex particularly comprising a Cas ortholog enzyme.

Abstract: The invention provides for delivery, engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are delivery systems and tissues or organ which are targeted as sites for delivery. Also 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 to ensure enhanced specificity for target recognition and avoidance of toxicity and to edit or modify a target site in a genomic locus of interest to alter or improve the status of a disease or a condition.

Abstract: Provided are a chimeric antigen receptor comprising an extracellular domain capable of binding to an antigen, a transmembrane domain and at least one intracellular domain, the chimeric antigen receptor being characterized in that an intracellular domain of a glucocorticoid-induced tumor necrosis factor receptor (GITR) is contained as the intracellular domain; a nucleic acid encoding the chimeric antigen receptor; a cell expressing the chimeric antigen receptor; and a method for producing the cell.

Abstract: The invention concerns the field of recombinant gene engineering. It concerns novel artificial introns and compositions comprising such introns as well as a method to improve expression of polypeptides from nucleic acids such as cloned genes, especially genes encoding antibodies and antibody derived fragments, and the production of various polypeptides in eukaryotic host cells using said novel artificial intron sequences.

Abstract: The present invention provides methods comprising both genetic and chemical means for the production of hepatocytes from a variety of cell sources, particularly pluripotent stem cells.

Abstract: A method for promoting entry of an agent (introduced agent) into a cell, the method comprising the step of complexing the introduced agent in the presence of an entry-promoting agent and then exposing to cells, wherein the entry-promoting agent comprises a linear and/or branched or cyclic polymonoguanide/polyguanidine, polybiguanide, analogue or derivative thereof according to the following Formula 1a & b. The method also provides a means for formation of nanoparticles formed between the entry promoting agent and the introduced agent.

Abstract: A transcription unit constituted by a polynucleotide including the hCMVie virus enhancer, the enhancer having the nucleotide sequence SEQ ID NO: 1, or a nucleotide acid having at least 70% sequence identity with the sequence SEQ ID NO: 1 and essentially having transcription activation properties, and the promoter region of Cyclin-Dependent Kinase 9 (CDK9), the promoter region having the nucleotide sequence SEQ ID NO: 2, or a nucleotide acid having at least 70% sequence identity with the sequence SEQ ID NO: 2 and essentially having a promoter activity.

Abstract: The identification and evaluation of mRNA and protein targets associated with mRNP complexes and implicated in the expression of proteins involved in common physiological pathways is described. Effective targets are useful for treating a disease, condition or disorder associated with the physiological pathway.

Abstract: Gene expression can be selectively modulated by contacting a cell with an oligomer that targets a gene region downstream of a ?3-UTR, thereby increasing or decreasing the expression of the target gene.

Abstract: The invention provides methods for treating asthma by using multiple rounds of administration of ISS over a period of time to confer long term disease modification.

Abstract: The present invention provides a baglike container for centrifugation that is mounted in a centrifuge to thereby allow centrifugation of a dispersion liquid accommodated therein. The baglike container for centrifugation is less likely to tear or break as a result of centrifugation by disposing a container wall surface of the baglike container so as to apply centrifugal force perpendicular to the container wall surface.

Abstract: The present inventors discovered that genes could be introduced specifically into trophectodermal cells with high efficiency, by infecting blastocysts with viral vectors carrying an arbitrary polynucleotide, or by using a nucleic acid transfection reagent in blastocysts, from which zona pellucida (extracellular matrix covering preimplantation early embryos to protect them from infection of viruses and the like) is removed. This method has no risk of infecting cells of the inner cell mass, which develops into a fetus in the future, with the introduced polynucleotide because the trophectoderm serves as a barrier. The present invention provides methods for introducing foreign genes into only placenta but not fetus, which enables rescue of genetically mutant animals from embryonic lethality due to placental abnormality and allows their birth. Furthermore, it is possible to analyze expression and effect of genes that regulate placental formation or placental function by using these methods.

Abstract: The invention relates to global transcription machinery engineering to produce altered cells having improved phenotypes.

Abstract: Described herein is a gene regulatory network based focused approach to cell transformation. The methods described herein allow for identification of circuit and sub-circuit repertoires for which modification in a starting cell type can result in generation of a transformed cell type in a durable and persistent manner, without requiring potentially deleterious genome modification. The described methods and compositions produced by the methods find widespread application in regenerative medicine applications.

Abstract: A cellular model is described for targeting dysregulation or inappropriate activation of the Sonic Hedgehog/Patched (SHH/PTCH) pathway. Also described, is a screening method using this cellular mod& to screen for pharmacological compounds that can treat or prevent skin cancer and, in particular, Basal Cell Carinoma (BCC) lesions.

Abstract: Compositions and methods are provided for making rat pluripotent and totipotent cells, including rat embryonic stem (ES) cells. Compositions and methods for improving efficiency or frequency of germline transmission of genetic modifications in rats are provided. Such methods and compositions comprise an in vitro culture comprising a feeder cell layer and a population of rat ES cells or a rat ES cell line, wherein the in vitro culture conditions maintain pluripotency of the ES cell and comprises a media having mouse leukemia inhibitor factor (LIF) or an active variant or fragment thereof. Various methods of establishing such rat ES cell lines are further provided. Methods of selecting genetically modified rat ES cells are also provided, along with various methods to generate a transgenic rat from the genetically modified rat ES cells provided herein. Various kits and articles of manufacture are further provided.

Abstract: A cellular model is described that targets dysregulation or inappropriate activation of the Sonic Hedgehog/Patched (SHH/PTCH) pathway. Also described, is a screening method using this cellular model to screen for pharmacological compounds that can treat or prevent skin cancer, in particular, Basal Cell Carcinoma, (BCC) lesions.

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 disclosure provides methods for increasing genome stability of an embryonic stem (ES) cell or induced pluripotent stem (iPS) cell, increasing telomere length in an ES or iPS cell, or both, for example by contacting an ES or iPS cell with an agent that increases expression of Zscan4 in the cell. Methods for increasing genome stability or increasing telomere length in a population of ES or iPS cells are provided, for example by selecting Zscan4+ ES or iPS cells from the population of ES or iPS cells (which can include both Zscan4+ and Zscan4? ES or iPS cells). Therapeutic methods of using ES or iPS cells expressing Zscan4 are also provided. Further provided are methods of treating cancer by administering a Zscan4 polynucleotide or Zscan4 polypeptide. Also provided are methods of inducing differentiation of isolated ES or iPS cells into germ cells.

Abstract: Photosensitive cardiac rhythm modulation structures and systems are described. A genetically-engineered tissue comprising a population of pacing cells expressing a photosensitive membrane transport mechanism that is responsive to light of a particular wavelength(s) combined with one or more of a light source, a power generator, and a sensor provides pacemaker and/or defibrillator function to a subject. The systems further provide in vitro model systems for electrophysiological studies.

Abstract: Methods and compositions for modifying stem cells using one or more ZFPs are disclosed. Such methods and compositions are useful for facilitating processes such as, for example, dedifferentiating cells, differentiating stem cells into the desired phenotype, propagating stem cells and/or facilitating cloning.

Abstract: Disclosed are methods for cell transfection and regulating cellular behavior. More particularly, the present disclosure relates to methods of non-viral cell transfection and regulating cellular behavior using mineral coatings that allow for the enhanced transfection of cells. The mineral coatings bind polynucleotides and provide a source of calcium and phosphate ions to enhance transfection. The present disclosure also provides a high throughput platform for screening non-viral transfection of cells. The methods of the present disclosure also provide an advantageous polynucleotide delivery platform because the mineral coatings may be deposited on various medical device materials after being specifically developed using the high throughput screening platform.

Abstract: This invention relates to nucleic acid molecules comprising at least one nucleic acid sequence encoding for a peptide or protein of interest, at least one nucleic acid sequence encoding for a selectable marker, and at least one IRES sequence, wherein the at least one IRES sequence is located between the at least one nucleic acid sequence encoding for the peptide or protein of interest and the at least one nucleic acid sequence encoding for the selectable marker. Furthermore, this invention relates to host cells comprising such nucleic acid molecule and to methods of recombinant protein expression using such host cells.

Abstract: This invention relates to immortalized avian cells, and to the use of these cells for the production of viruses. The cells according to the invention are particularly useful for the production of recombinant viral vectors which can be used for the preparation of therapeutic and/or prophylactic compositions for the treatment of animals and more particularly humans.

Abstract: A method for the production of adeno-associated virus stocks and recombinant adeno-associated virus stocks that are substantially free of contaminating helper virus is described. The method utilizes transfection with helper virus vectors to replace the infection with helper virus used in the conventional method.