Abstract: Methods and composition of induction of pluripotent stem cells and other desired cell types are disclosed. For example, in certain aspects methods for generating essentially vector-free induced pluripotent stem cells are described. Furthermore, the invention provides induced pluripotent stem cells and desired cell types essentially free of exogenous vector elements with the episomal expression vectors to express differentiation programming factors.

Abstract: The present invention relates to novel insertion sites useful for the integration of exogenous sequences into the Modified Vaccinia Ankara (MVA) virus genome. The present invention further provides plasmid vectors to insert exogenous DNA into the genome of MVA. Furthermore, the present invention provides recombinant MVA comprising an exogenous DNA sequence inserted into the new insertion site as medicine or vaccine.

Abstract: This invention relates to the field of biotechnology or genetic engineering. Specifically, this invention relates to the field of gene expression. More specifically, this invention relates to novel substitution mutant receptors and their use in a Group H nuclear receptor-based inducible gene expression system and methods of modulating the expression of a gene in a host cell for applications such as gene therapy, large scale production of proteins and antibodies, cell-based high throughput screening assays, functional genomics and regulation of traits in transgenic organisms.

Abstract: The present invention relates to an enhancer which functions only in human brain and/or spinal cord motor neurons, where the enhancer comprises a nucleotide sequence of SEQ ID NO: 5, SEQ ID NO: 10, or SEQ ID NO: 16. The enhancer can be utilized as part of a nucleic acid construct which also has a nucleic acid encoding a marker protein or a therapeutic protein, a 3? control region, and, optionally, a basal promoter, where these components are positioned with respect to one another to permit expression of the marker protein or the therapeutic protein. The enhancer of the present invention is useful in a method of isolating an enriched or purified population of motor neurons from a mixed population of human brain and/or spinal cells. In addition, the enhancer of the present invention can be used in a method of therapeutically targeting motor neurons.

Abstract: The presently disclosed subject matter provides methods and compositions for modulating gene expression in myocytes. Also provided are cells comprising the compositions of the presently disclosed subject matter.

Abstract: Disclosed are tyrosine-modified rAAV vectors, as well as infectious virions, compositions, and pharmaceutical formulations that comprise them. Also disclosed are methods of preparing and methods for using the disclosed tyrosine-phosphorylated capsid protein mutant rAAV vectors in a variety of diagnostic and therapeutic applications including in vivo and ex vivo gene therapy, and large-scale production of rAAV vectors.

Abstract: The present invention provides Sendai virus vectors in which genes that encode reprograming factors for inducing pluripotent stem cells are incorporated in a specific order, compositions comprising these vectors for gene delivery to be used in the induction of pluripotent stem cells, and uses thereof. Incorporation of the KLF gene, OCT gene, and SOX gene in a specific order into a single Sendai virus vector successfully and significantly increased the efficiency of pluripotent stem cell induction. Loading multiple reprogramming factors into a single vector can further increase the induction efficiency of pluripotent stem cells while reducing the number of necessary vectors.

Abstract: The present invention provides an induced cancer cell capable of self-replication in vitro which is useful in cancer therapy research and the research for cancer-related drug discovery, processes for production thereof, cancer cells induced by the malignant cells, and applications of these cells. The present invention provides an induced cancer stem cell capable of proliferation (self-replication) in vitro, wherein the induced cancer stem cell has the following two characteristics: (1) expressing the six genes (self-renewal related genes) POU5F1, NANOG, SOX2, ZFP42, LIN28, and TERT selected from a certain group of genes; and (2) having an aberration which is either (a) a mutation in an endogenous tumor suppressor gene or (b) increased expression of an endogenous cancer-related gene.

Abstract: Stem cell reprogramming genes cloned into a single sustained expression-type Sendai viral vector are shown to reprogram differentiated somatic cells into induced pluripotent stem (iPS) cells without integration of vector sequences into the host cell's genome. The genes are transduced into normal differentiated somatic cells via infection with recombinant Sendai virus. After expression of the reprogramming genes and subsequent induction of pluripotency, the vector genome RNA including the reprogramming genes is removed from the cell to establish an iPS cell that is genetically identical to the parent somatic differentiated cell thus reducing the risk of tumorigenic transformation caused by random integration of vector sequences into the host genome. The method promises to provide safe, autologous iPS cells that can be used for human cell replacement and regeneration therapeutic applications.

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: Substantially avirulent forms of atypical porcine reproductive and respiratory syndrome (PRRS) virus and corresponding vaccines are provided which result from cell culture passaging of virulent forms of PRRS. The resultant avirulent atypical PRRS virus is useful as a vaccine in that PRRS specific antibody response is elicited by inoculation of host animals, thereby conferring effective immunity against both previously known strains of PRRS virus and newly isolated atypical PRRS virus strains. The preferred passaging technique ensures that the virus remains in a logarithmic growth phase substantially throughout the process, which minimizes the time required to achieve attenuation. The present invention also provides diagnostic testing methods which can differentiate between animals infected with field strains and attenuated strains of PRRSV.

Abstract: Disclosed are methods for producing class-switched, affinity-matured antibodies which include enriching an immunized cell population for GL7-positive cells and activating the enriched cells. The methods may be used to improve the efficiency of obtaining immortalized antigen-specific plasma cells or to improve the quality of molecularly cloned Ig heavy and light chains.

Abstract: The invention provides viral vectors (e.g., herpes viral vectors) and methods of using these vectors to treat disease.

Abstract: We have disclosed an induced pluripotent stem cell and the method of preparing the induced pluripotent stem cell from a human kidney-derived cell. More particularly, we have disclosed a human kidney-derived iPS cell which may be differentiated into cells of ectoderm, mesoderm, and endoderm lineages.

Abstract: The present invention relates to methods for obtaining stem cells from mammalian cadavers, methods for obtaining or purifying stem cells from a sample likely to contain non-stem cells, methods of regeneration of injured tissues and methods of treatment.

Abstract: Nucleases and methods of using these nucleases for modification of an HPRT locus and for increasing the frequency of gene modification at a targeted locus and clones and for generating animals.

Abstract: Modified antigen presenting cells provided herein have improved lifespan and immunogenicity compared to unmodified antigen presenting cells, and are useful for immunotherapy. The modified antigen presenting cells express an altered protein kinase, referred to herein as “Akt.” The altered Akt associates with the cell membrane with greater frequency than unaltered Akt, and is referred to herein as “membrane-targeted Akt.

Abstract: A method for generating induced pluripotent stem (iPS) cells from isolated hair follicles is disclosed. The method comprises: a. culturing isolated hair follicle keratinocytes on a layer of feeder cells, so as to generate colonies of hair follicle keratinocytes; b. detaching the colonies of hair follicle keratinocytes from the feeder cells so as to generate detached keratinocytes; c. infecting the detached keratinocytes with a virus comprising a nucleic acid molecule encoding at least one dedifferentiation factor so as to generated infected keratinocytes; and d. culturing the infected keratinocytes on a layer of feeder cells in a culture medium until iPS cells are formed, thereby generating iPS cells. Populations and uses of the iPS cells are also disclosed.

Abstract: The present invention relates to tumor cell-based vaccines and methods of using same, wherein the vaccines are based on naturally immune privileged tumor cells that have been genetically modified to express MHC-II restricted peptides derived from endogenously encoded tumor antigens, activate CD4+ T-lymphocytes, provide an array of antigens to which the host is not tolerized and/or induce immunity against the originating tumor cells as well as against metastatic tumor cells.

Abstract: Nucleases and methods of using these nucleases for modification of an HPRT locus and for increasing the frequency of gene modification at a targeted locus and clones and for generating animals.

Abstract: Provided is a construct comprising (i) a nucleotide sequence which encodes tyrosine hydroxylase (TH), (ii) a nucleotide sequence which encodes GTP-cyclohydrolase I (CH1) and (iii) a nucleotide sequence which encodes Aromatic Amino Acid Dopa Decarboxylase (AADC) wherein the nucleotide sequence encoding TH is linked to the nucleotide sequence encoding CH1 such that they encode a fusion protein TH-CH1. Also provided is a construct comprising (i) a nucleotide sequence which encodes tyrosine hydroxylase (TH), (ii) a nucleotide sequence which encodes GTP-cyclohydrolase I (CH1) and (iii) a nucleotide sequence which encodes Aromatic Amino Acid Dopa Decarboxylase (AADC) wherein the nucleotide sequence encoding AADC is linked to the nucleotide sequence encoding TH such that they encode a fusion protein AADC-TH or TH-AADC. Further provided is a viral vector comprising such nucleotide sequences and its use in the treatment and/or prevention of Parkinson's disease.

Abstract: A highly controlled and precise system, device and method for tissue and cellular alteration and treatment below or at surfaces with a laser. The present invention is characterized by ultra low levels of collateral damage as defined by physiologically relevant tests that measure tissue viability. The operation of the present invention is based on spectrally confining the interaction between laser energy and a targeted tissue including an essential element for physiologically relevant tests for monitoring tissue viability.

Abstract: This invention relates to modified parvovirus inverted terminal repeats (ITRs) that do not functionally interact with wild-type large Rep proteins, synthetic Rep proteins that functionally interact with the modified ITRs, and methods of using the same for delivery of nucleic acids to a cell or a subject. The modifications provide a novel Rep-ITR interaction that limits vector mobilization, increasing the safety of viral vectors.

Abstract: Disclosed is a method for introducing a gene into a target cell using a retrovirus vector, which is simple and highly efficient. Specifically disclosed is a method for introducing a gene into a target cell using a retrovirus vector, which comprises the steps of (a) placing a liquor containing a retrovirus vector having a foreign gene carried thereon into a culture vessel on which a retrovirus-binding substance has been immobilized, and incubating the liquor at a temperature lower than 25° C. for 4 hours or longer, thereby producing a culture vessel having the retrovirus vector bound thereto, and (b) adding a target cell to the culture vessel that has been produced in step (a) and incubating the culture vessel. The gene introduction method is simple and highly efficient, and is useful particularly in the fields of medicine, cell technology, gene technology, embryologic technology and the like.

Abstract: Methods for screening compounds to treat an oncological disorder regulated through a tumor-inducing pathway are provided. The compounds are administered to non-human animal subjects having a disease model, so that the subjects display pathology symptoms that correspond to the oncological disorder in humans. The subjects carry a regulatable transgene expression, of which is associated with tumor formation, and further carry regulatable genes for suppression of tumor formation. The disease-pathology symptoms are induced using a site-specific recombination system to induce expression of the transgene associated with tumor formation and negatively regulate or eliminate the genes for suppression of the tumor formation. The methods further involve analyzing tumor formation in subjects administered the compound and comparing appearance and amount of tumors in the subjects administered the compound with control subjects not administered the compound.

Abstract: The present invention relates to methods and compositions for treatment of cardiovascular and peripheral vascular diseases using ex vivo and in vivo gene delivery technologies. One aspect of the present invention relates to a method for treating a vascular disease by introducing a DNA sequence encoding a TM protein or its variant into a segment of a blood vessel in vivo using a gutless adenovirus vector. Another aspect of the present invention is to provide a method to deliver a gutless adenovirus vector carrying a DNA sequence encoding a TM protein or its variant using a stent.

Abstract: The present invention relates to use of synthetic factors in reprogramming somatic cells to become induced pluripotent stem cells and other cell lineages. Specifically, the present application relates to fusion proteins containing proteins encoded by cell totipotency-related genes and transcription regulatory domains, their coding sequences, expression vectors, and compositions. The present application also relates to methods for reprogramming somatic cells to become induced pluripotent stem cells and other cell lineages, and cells containing the fusion proteins or the coding sequences.

Abstract: The nucleic acid sequences of adeno-associated virus (AAV) serotype 1 are provided, as are vectors and host cells containing these sequences and functional fragments thereof. Also provided are methods of delivering genes via AAV-1 derived vectors.

Abstract: Recombinant adeno-associated viral (AAV) capsid proteins are provided. Methods for generating the recombinant adeno-associated viral capsid proteins and a library from which the capsids are selected are also provided.

Abstract: Novel hexon isolated from simian adenovirus serotype 19 encoded in the polynucleotide defined as SEQ ID NO: 3, hepervariable region thereof, chimeric adenovirus comprising the same, and therapeutic use thereof provides a solution to the problem of safety and effective systemic treatment for developing gene therapeutic agents using adenovirus.

Abstract: Methods are provided for producing cells within a lineage (lineage restricted cells) from post-mitotic differentiated cells of the same lineage ex vivo and in vivo, and for treating a subject in need of tissue regeneration therapy by employing these lineage-restricted cells. In addition, the production of lineage restricted cells from postmitotic tissues derived from patients with diseases allows for a characterization of pathways that have gone awry in these diseases and for screening of drugs that will ameliorate or correct the defects as a means of novel drug discovery. Also provided are kits for performing these methods.

Abstract: Methods for producing engineered induced pluripotent stem (iPS) cells are provided comprising introducing a first nucleic acid into somatic cells for integration into their genome and reprogramming the cells to produce engineered iPS cells having the nucleic acid integrated into their genome. For example, in certain aspects the cells are reprogrammed by introduction of a genetic element that expresses one or more reprogramming factor and culturing of the cells under conditions sufficient to produce reprogrammed cells.

Abstract: The invention provides for methods of producing pancreatic precursor cells and insulin-producing cells from bone marrow. In various embodiments, bone marrow derived stem cells are differentiated into pancreatic precursor cells and insulin-producing cells. In various embodiments, bone marrow derived stem cells are artificially induced to express VEGF and/or PDX-1. These cells can be used to treat or ameliorate diabetes or symptoms of diabetes.

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 present invention provides duplexed parvovirus vector genomes that are capable under appropriate conditions of forming a double-stranded molecule by intrastrand base-pairing. Also provided are duplexed parvovirus particles comprising the vector genome. Further disclosed are templates and methods for producing the duplexed vector genomes and duplexed parvovirus particles of the invention. Methods of administering these reagents to a cell or subject are also described. Preferably, the parvovirus capsid is an AAV capsid. It is further preferred that the vector genome comprises AAV terminal repeat sequences.

Abstract: The present invention provides new lentiviral vectors that include an anti-repressor element (ARE) and, optionally, a scaffold attachment region (SAR). The lentiviral vectors provide expression of a heterologous nucleic acid in at least 50% of the cells of multiple cell types when used for lentiviral transgenesis. In certain embodiments of the invention the heterologous nucleic acid encodes an RNAi agent such as an shRNA. The invention further provides transgenic nonhuman animals generated using a lentiviral vector that includes an ARE and optional SAR. In addition, the invention provides a variety of methods for using the vectors including for achieving gene silencing in eukaryotic cells and transgenic animals, and methods of treating disease. The invention also provides animal models of human disease in which one or more genes is functionally silenced using a lentiviral vector of the invention.

Abstract: The present invention relates to an improved cancer therapy comprising co-administration with the E1A 1-80 transcription-repression domain activity. In addition, E1A 1-80 can act as a monotherapy against cancers that express elevated HER2/Neu or in combination with anti-HER2/Neu, chemo- or radiotherapeutic treatments.

Abstract: Provided is dental stem cell comprising an Oct3/4 transgene. Also provided is a method of making a pluripotent stem cell. Additionally, a method of preparing an insulin-secreting cell is provided. Further provided is an insulin-secreting cell prepared by that method. A method of preparing a chondrocyte-like cell is also provided, as is a chondrocyte-like cell prepared by that method. Additionally provided is a method of preparing a myocyte-like cell. Also, a myocyte-like cell prepared by that method is provided. A method of preparing a hair follicle-like cell is additionally provided, as is a hair follicle-like cell prepared by that method. A method of preparing a neuron-like cell is additionally provided, as is a neuron-like cell prepared by that method.

Abstract: The present invention provides methods and compositions for enhanced transduction of an adeno-associated virus (AAV) vector comprising a heterologous nucleic acid of interest wherein the AAV vector genome is oversized relative to a wild type AAV genome by employing a proteasome inhibitor.

Abstract: Methods and devices for causing uptake of materials by cells, temporary using local chemical environment modification. The modification may be caused chemically by reducing pH. The uptake method is passive and does not require bioactivity of the cells.

Abstract: Disclosed are methods of differentiating stem cells into muscle cells by growing the cells in a myogenic culture medium. The differentiated cells can be used as a source of cells for transplantation in a patient in need thereof.

Abstract: A method and vectors for controlling blood glucose levels in a mammal are disclosed. In one embodiment, the method comprises the steps of: treating the hepatocyte cells of a patient with a first, second or third vector, wherein the first vector comprises a promoter enhancer, glucose inducible regulatory elements, a liver-specific promoter, a gene encoding human insulin with modified peptidase and an albumin 3?UTR and lacks an HGH intron, wherein the second vector comprises an HGH intron, glucose inducible regulatory elements, a liver-specific promoter, a gene encoding human insulin with modified peptidase site and an albumin 3?UTR and lacks a promoter enhancer, wherein the third vector comprises an HGH intron, glucose inducible regulatory elements, a liver-specific promoter, a gene encoding human insulin with modified peptidase site, an albumin 3?UTR and a promoter enhancer and observing the patient's insulin levels, wherein the patient's insulin levels are controlled.

Abstract: Disclosed herein are methods and compositions for inactivating CCR-5 genes, using zinc finger nucleases (ZFNs) comprising a zinc finger protein and a cleavage domain or cleavage half-domain. Polynucleotides encoding ZFNs, vectors comprising polynucleotides encoding ZFNs, such as adenovirus (Ad) vectors, and cells comprising polynucleotides encoding ZFNs and/or cells comprising ZFNs are also provided.

Abstract: The present invention is concerned with methods for reprogramming of mammalian somatic cells and in particular to reprogramming of mature mammalian somatic cells into multi-potent precursor cells.

Abstract: Methods for producing recombinant cell populations are disclosed. The disclosed methods may be used to produce therapeutic polyclonal proteins.

Abstract: The RNAi target sequences, which could be used for treating AIDS through targeting HIV. Based on the target sequences, recombinant expression vectors, packaging vectors and cells were constructed, which express siRNA and/or miRNA and/or ribozyme and/or antisense oligonucleotide for targeting HIV. And the applications of said recombinant expression vectors, packaging vectors and cells in preparing medicament for treating AIDS.

Abstract: The present invention provides methods for modulating expression of endogenous cellular genes using recombinant zinc finger proteins.

Abstract: The present invention is directed to methods and compositions that are effective in the inhibition of viral replication. In particular, the methods and compositions are effective at interfering with the activity of host cell proteins required in viral replication. For example, an embodiment of the invention is directed to inhibition of flavivirus replication wherein the replication is effected by changing the normal interactions of the host cell protein TIAR or TIA-1.

Abstract: The present invention is directed to new compositions uses thereof and related methods for the treatment of a motoneuron disease or disorder. In particular, the invention relates to the new use of IFN? antagonists or viral vectors, uses, compositions thereof and related methods for the treatment of motoneuron disease or disorder such as ALS.

Abstract: Subject of the invention are peptides corresponding to a fragment of amino acids 240-290 of human prostatic acid phosphatase. The invention also relates to nucleic acids, antibodies, medicaments and diagnostics and their use and use of the peptides for the treatment and diagnosis of viral diseases, especially HIV disease.