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.

Abstract: Disclosed is a method for coexpressing IL-12 (interleukin-12) and IL-23 (interleukin-23), which comprises the steps of: (a) preparing vectors comprising monocistronic expression constructs of each of nucleotide sequences encoding the p35 subunit, the p40 subunit and the p19 subunit, or preparing a vector comprising a polycistronic expression construct of nucleotide sequences encoding the p35 subunit, the p40 subunit and the p19 subunit; (b) transforming the expression constructs into a host cell; and (c) culturing the transformed host cell to obtain IL-12 and IL-23, a vector for coexpressing IL-12 and IL-23, and a pharmaceutical anti-tumor composition comprising the vectors.

Abstract: This invention relates to a process for producing a Simian Immunodeficiency Virus (SIV) encoding a heterologous gene, which process comprises infecting a host cell with a first vector which is capable of producing SIV capsid and a second vector comprising a Human Immunodeficiency Virus type 2 (HIV-2) packaging signal sufficient to package the second vector in the SIV capsid and a heterologous gene capable of being expressed by the vector; and culturing the host cell.

Abstract: The present invention relates to a protein containing a modified DDR (Discoidin Domain Receptor) 2 cytosolic tyrosine kinase domain having an increased autophosphorylation and tyrosine kinase activity; a method for preparing a large amount of a protein containing DDR2 cytosolic tyrosine kinase domain, having an increased autophosphorylation and tyrosine kinase activity by inducing phosphorylations of tyrosines by a co-expression with Src or Src related proteins in host cells, or by H2O2 processing of host cells, or a site directed mutation modifying at least one of tyrosines to other amino acid; and a use thereof as a target material in developing medical drugs for treating a disease caused by an excessively activated DDR2 autophosphorylation and tyrosine kinase activity.

Abstract: Nucleic acid delivery vehicles and methods of their use are provided. One embodiment provides a virus having a lipid-polymer conjugate intercalated into the virus's membrane. The lipid-polymer conjugate includes a biocompatible polymer having first and second ends, a lipid conjugated to the first end, and a targeting moiety conjugated to the second end. The lipid is preferably a multi-chain lipid. The virus encodes one or more polypeptides that can help reduce or mitigate one or more symptoms of a disease or pathology. The lipid-polymer conjugate advantageously reduces non-specific binding of the virus while the targeting moiety enhances binding to specific cells or tissues.

Abstract: The present invention relates to methods of host cell transduction utilising ecotropic retroviral vector particles. The retroviral vector particle may comprise an envelope of Friend murine leukaemia virus, in particular the envelope encoded by molecular clone PVC-211 and the host cell may be engineered to recombinantly express the Reel receptor. The retroviral vector particles and methods of the invention can be used to introduce expressible polynucleotide sequences of interest into host cells with high efficiency. This results in protein production methods with higher yield (mg/L) and a reduction in manufacturing costs that could be used in a range of applications including for example, the production of therapeutic proteins, vaccines and antibodies.

Abstract: Application of a virus with poloxamer alone onto atria results in diffuse epicardial gene transfer with negligible penetration into the myocardium. Progressive increases in protease concentration, however, allow transmural gene transfer. After protease exposure, echocardiographic left atrial diameter does not change. Left atrial ejection fraction decreases on post-operative day 3, but returns to baseline by day 7. At appropriate protease concentrations, tissue tensile strength is unaffected by the procedure. Transmural atrial gene transfer can be effected using this direct “painting” method.

Abstract: A method for enhancing repair of damaged mammalian tubular epithelial cells involves delivering to the tubular epithelial cells of a subject in need thereof a composition comprising an adeno-associated virus (AAV) comprising an AAV capsid having an amino acid sequence of a selected AAV serotype, and a minigene having AAV inverted terminal repeats and a Sec10 gene operatively linked to regulatory sequences that direct expression of Sec10 in the epithelial cells. In one embodiment, delivery is accomplished by retrograde intrauretal injection. In an embodiment the AAV vector includes a capsid of AAV serotype 2/8. Therapeutic compositions containing such AAV are provided.

Abstract: Disclosed is a method for preparation of transmissible spongiform encephalopathy (TSE) susceptible cells, and such cells may be efficiently used in diagnosis of TSE, etiology studies and development of novel therapeutics, etc.

Abstract: Disclosed are: a gene transduction method for use in the induction of the differentiation of stem cells such as ES cells or iPS cells into hepatocytes effectively; stem cells into each of which a gene useful for the induction of the differentiation into hepatocytes is introduced; and hepatocytes produced from stem cells each having the gene introduced therein. A specific gene can be introduced into stem cells such as ES cells or iPS cells using an adenovirus vector. The effective induction of the differentiation into hepatocytes can be achieved by introducing the gene. Specifically, the effective induction of the differentiation of stem cells such as ES cells or iPS cells into hepatocytes can be achieved by introducing at least one gene selected from HEX gene, HNF4A gene, HNF6 gene and SOX17 gene into the stem cells.

Abstract: Methods to improve the tropism or other features of a virus are disclosed. Such methods can be used to prepare, e.g., DNA or plasmid libraries of variants of a gene encoding a viral capsid or envelope protein having a randomly inserted restriction site, libraries of viral clones with such variant genes with a randomly inserted restriction site or polypeptide sequence targeting a receptor expressed by a specific type of mammalian cells. Described are also methods to prepare mosaic viruses, i.e., viral particles wherein copies of one or more capsid or envelope proteins originate from different sources. These methods can be used to prepare mosaic viruses of a specific mixture of wild-type and mutant proteins, or of different types of mutant proteins.

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

Abstract: A reprogramming gene-loaded Sendai viral vector comprising Sendai virus genes and reprogramming genes, wherein the Sendai virus genes include an NP gene, P/C gene, M gene, F gene, HN gene and L gene, wherein each of the M gene, the F gene and the FIN gene is from a Sendai virus strain Cl.151-derived gene and wherein at least one of the M gene, the F gene and the HN gene is functionally deleted and the L gene encodes the amino-acid sequence of the L protein in which the amino-acid residue at position 1618 is valine and a method of producing the same.

Abstract: The present invention relates to a composition for improving the migration potential of a stem cell, a method for evaluating the migration potential of a stem cell and a method for screening an adjuvant of cell therapy improving the migration potential of a stem cell. The present invention may be effectively used for enhancing the efficacy of neurological disease-treatment by inducing therapeutic stem cells to migrate efficiently to the lesion site.

Abstract: Fully defined media that support pluripotent cell viability, proliferation, cloning, and derivation, as well as methods and compositions including these media are described. Methods for deriving iPS cells from adult individuals under defined, xeno-free conditions are also described.

Abstract: The invention relates to the field of stem cells and, specially, to the reprogramming of adult somatic cells; to obtain pluripotent cells by the transfection of specific genes. Thus, the invention provides induced pluripotent stem cells (iPS) and methods of obtaining and using them.

Abstract: The present invention relates to an intracellular viral vector delivery method employing an iron ion/viral vector composite. The iron ion/viral vector composite according to the present invention is not dependent on the expression of CAR and so improves the efficiency of delivery of viral vectors and gene expression in cells of diverse types, and has an outstanding virus-neutralizing antibody escape performance, exhibits little cytotoxicity and is outstandingly stable even when subjected to iron ion processing at low concentration, and hence can be used to advantage in recombinant viral vaccine compositions.

Abstract: Recombinant viral vectors, especially parvovirus vectors such as adeno-associated virus (AAV) vectors, capable of enhanced expression of heterologous sequences, and methods for their construction and use, are provided. The vectors have a structure, or are capable of rapidly adopting a structure, which involves intrastrand base pairing of at least one region in a heterologous sequence.

Abstract: The present invention provides transgenic, large non-human animal models of diseases and conditions, as well as methods of making and using such animal models in the identification and characterization of therapies for the diseases and conditions.

Abstract: The present invention provides recombinant replication-defective adenoviral vectors derived from chimpanzee adenoviruses and methods for generating recombinant adenoviruses in human E1-expressing cell lines. The invention also provides compositions and methods suitable for use for the delivery and expression of transgenes encoding immunogens against which a boosted immune response is desired. The invention further provides methods of generating clinical grade vector stocks suitable for use in humans. In a particular embodiment the invention contemplates the use of vectors comprising transgenes which encode tumor associated antigens in vaccines and pharmaceutical compositions for the prevention and treatment of cancer.

Abstract: A population of iPS cells derived from somatic cells from a spinal muscular atrophy patient is disclosed. In one embodiment of the invention, the cells have been cultured to produce neural cells. In another embodiment, the invention is a method of testing compounds for their ability to modify cellular SMN levels comprising the steps of obtaining a population of iPS cells derived from a spinal muscular atrophy patient or cells derived from the iPS cells, and examining the effect of a test compound on SMN levels.

Abstract: The present invention provides a method for preparing a non-adenoviral target virus or target proteins utilizing a potent expression cell line having stably integrated into its genome a gene encoding a specific heterologous regulator protein.

Abstract: Disclosed is a viral vector comprising (a) a cDNA of a recombinant viral RNA having at least the N gene, the X gene, the P gene, and the L gene of a Borna disease virus genome in the same order as that in the Borna disease virus genome, and having a sequence in which a foreign gene is inserted into the untranslated region connected to the downstream of the open reading frame of the P gene, (b) a DNA encoding a ribozyme, and (c) a promoter sequence, each being disposed in a position in which (b) is placed upstream and downstream of (a), and (a) and (b) are placed downstream of (c).

Abstract: The invention relates to novel insertion sites useful for the integration of HIV DNA sequences into the MVA genome, and to the resulting recombinant MVA derivatives.

Abstract: A recombinant herpesvirus, a method for producing the recombinant herpesvirus, and a pharmaceutical composition comprising the recombinant herpesvirus, are provided with a method for producing a recombinant herpesvirus using a BAC vector sequence. In addition, a vector comprising a herpesvirus genomic gene and a BAC vector sequence, a cell comprising the vector, and a nucleic acid cassette comprising a fragment, which is capable of homologous recombination with a herpesvirus genome, and a BAC vector sequence, are provided.

Abstract: Methods for expansion of antigen-specific T cells are provided. Said methods include following steps: generating antigen-specific T cells by stimulation of T cells with antigen A; introducing genes encoding immune recognition molecule specific to major histocompatibility complex (MHC) molecule bound with a peptide derived from antigen B into the antigen A specific T cell to produce bi-specific T cells recognizing both target cells expressing antigen A peptide associated MHC and target cells expressing antigen B peptide associated MHC; stimulating the bi-specific T cells by antigen A for expansion of the bi-specific T cells in vitro or in vivo. Methods of the present invention can be applied to expand various of T cells with specific to cancer cells with tumor antigen peptide loaded MHC molecules for adoptive therapy against unmet medical need such as tumors etc.

Abstract: A method for producing a chimaeric human papillomavirus (HPV) L1 polypeptide containing a heterologous peptide, and in particular, a HPV L2 peptide comprising the steps of introducing a DNA sequence coding for the heterologous peptide into a DNA sequence coding for the L1 polypeptide; introducing the DNA sequence including the sequences for the L1 polypeptide and heterologous peptide into a host cell in which the DNA sequence can be expressed; causing expression of the DNA sequence; and recovering the resulting chimaeric L1 polypeptide which includes the heterologous peptide. The invention also describes a vector for use in the method, a host cell containing the vector, and a vaccine including the chimaeric HPV L1 polypeptide produced according to the method.

Abstract: Methods for producing interfering RNA molecules in mammalian cells are provided. Therapeutic uses for the expressed molecules, including inhibiting expression of HIV, are also provided.

Abstract: Provided herein are compositions and methods for gene and etiology-nonspecific and circuit-specific treatment of diseases, utilizing vectors for delivery of light-sensitive proteins to diseased and normal cells and tissues of interest.

Abstract: Chimeric alphaviruses and alphavirus replicon particles are provided, including methods of making and using same. Specifically, alphavirus particles are provided having nucleic acid molecules derived from one or more alphaviruses and structural proteins (capsid and/or envelope) from at least two or more alphaviruses. Methods of making, using, and therapeutic preparations containing the chimeric alphavirus particle, are disclosed.

Abstract: The disclosure provide cell lines and methods for the production of vectors and viral particles useful in gene therapy.

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 said new insertion site as medicine or vaccine.

Abstract: A method for treating an ocular disorder characterized by the defect or absence of a normal gene in the ocular cells of a human or animal subject involves administering to the subject by subretinal injection an effective amount of a recombinant adeno-associated virus carrying a nucleic acid sequence encoding the normal gene under the control of a promoter sequence which expresses the product of the gene in the ocular cells. The ocular cells are preferably retinal pigment epithelial (RPE) cells, and the gene is preferably an RPE-specific gene, e.g., RPE65. The promoter is one that can express the gene product in the RPE cells. Compositions for subretinal administration are useful in this method.

Abstract: The invention relates to the discovery that mutations of serine residues of an AAV capsid results in significantly greater transfection efficiency than the wild type AAV2 virus. In one embodiment, the present invention provides a method of improving efficiency of gene transfer and/or gene therapy to a cell by inhibiting phosphorylation of one or more serine residues of a virus capsid protein, where the inhibition of the phosphorylation of one or more serine residues results in a decrease of ubiquitination of the virus capsid protein in the cell. In another embodiment, one of the one or more serine residues is Serine 264. In another embodiment, the Serine 264 residue is mutated to Alanine (S 264 A).

Abstract: Comparative gene analysis (CGA) was combined with pathway visualization software to identify a positive correlation between AAV6 transduction and epidermal growth factor receptor (EGFR) expression. It was found that EGFR is necessary for vector internalization and functions as a co-receptor for AAV6. The identification and characterization of AAV6's requirement of EGFR expression for high transduction activity has allowed construction of recombinant AAV6 vectors which are capable of targeting and killing specific types of head and neck tumors that because of this high EGFR activity, were until now, refractory to current therapies.

Abstract: Restenosis in a subject can be treated by administering to a tissue, e.g., a blood vessel, of the subject an agent that increases SERCA activity. For example, a stent that is coated with the agent can be introduced into a blood vessel.

Abstract: The present invention relates to compositions of virus-like particles for the introduction of RNA-interference (RNAi-) inducing molecules into eukaryotic cells and methods for the cell type-specific transduction of a plurality of eukaryotic cells with RNAi-inducing molecules. The present invention furthermore relates to methods for a diagnosis, prevention and/or treatment of diseases or disease states associated with an increased expression rate of at least one endogenous gene, and/or with the undesired expression of at least one endogenous gene and/or foreign nucleic acids, in particular viral nucleic acids.

Abstract: An antisense molecule capable of binding to a selected target site to induce exon skipping in the dystrophin gene, as set forth in SEQ ID NO: 1 to 202.

Abstract: The method is based on the use of expression vectors coding for the sense and anti-sense mRNA of the Phase I and Phase II drug biotransformation enzymes showing a greatest variability in humans for transforming cells expressing reductase activity. Such vectors can modulate (increase or decrease) the individualized expression of an enzyme without affecting the other enzymes. This singular cell model can reproduce in vitro the metabolic idiosyncrasy of humans. It is applicable in the study of development of new drugs, specifically in the study of metabolism, potential idiosyncratic hepatotoxicity, medicament interactions, etc., of new drugs.

Abstract: The present invention is directed to methods for enhanced retroviral delivery of a nucleic acid to a target cell in vitro, ex vivo or in vivo, which involves increasing infectivity of a retrovirus carrying a transgene of interest to a target cell. In one particular aspect the invention relates to a method for increasing retroviral infectivity of target cells comprising culturing packaging cells transfected with retroviral vector containing a transgene of interest in medium containing a glucocorticoid receptor agonist or analog or derivative thereof present in the medium in an amount effective to increase titer of propagated retrovirus; and subsequently culturing a target cell in medium comprising the propagated retrovirus from a) and a glucocorticoid receptor antagonist or analog or derivative thereof present in the medium in an amount effective to increase target cell sensitivity to infection by the propagated retrovirus.

Abstract: It is described in vitro methods for expanding, detecting or isolating rare populations of antigen specific memory T cells. It is also described an in vitro method for obtaining a genetically modified memory T cell population. Uses of cells so obtained are also disclosed.

Abstract: The present invention provides methods of generating a mammalian cell that is homozygous at a locus of interest, as well as cells made by the method. The present invention further provides methods of using the cells.

Abstract: A recombinant vector comprises simian adenovirus sequences and a heterologous gene under the control of regulatory sequences. A cell line which expresses simian adenovirus gene(s) is also disclosed. Methods of using the vectors and cell lines are provided.

Abstract: An antisense molecule capable of binding to a selected target site to induce exon skipping in the dystrophin gene, as set forth in SEQ ID NO: 1 to 202.

Abstract: The invention relates to novel insertion sites useful for the integration of HIV DNA sequences into the MVA genome, and to the resulting recombinant MVA derivatives.

Abstract: The present invention provides AAV capsid proteins (VP1, VP2 and/or VP3) comprising a modification in the amino acid sequence in the three-fold axis loop 4 and virus capsids and virus vectors comprising the modified AAV capsid protein. In particular embodiments, the modification comprises a substitution of one or more amino acids at amino acid positions 585 to 590 (inclusive) of the native AAV2 capsid protein sequence or the corresponding positions of other AAV capsid proteins. The invention also provides methods of administering the virus vectors and virus capsids of the invention to a cell or to a subject in vivo.

Abstract: Recombinant viral vectors, especially parvovirus vectors such as adeno-associated virus (AAV) vectors; capable of enhanced expression of heterologous sequences, and methods for their construction and use, are provided. The vectors have a structure, or are capable of rapidly adopting a structure, which involves intrastrand base pairing of at least one region in a heterologous sequence.

Abstract: The present invention relates to a method for producing herpes simplex virus (HSV) amplicon particles which includes co-transfecting a host cell with the following: (i) an amplicon vector comprising an HSV origin of replication, an HSV cleavage/packaging signal, and a heterologous transgene expressible in a patient, (ii) one or more vectors individually or collectively encoding all essential HSV genes but excluding all cleavage/packaging signals, and (iii) a vhs expression vector encoding a virion host shutoff protein; and then isolating HSV amplicon particles produced by the host cell, the HSV amplicon particles including the transgene. Also disclosed are a system and a kit for preparing HSV amplicon particles, HSV amplicon particles prepared according to the process of the present invention, and their use.

Abstract: This disclosure is directed to the methods of enhancing hematopoietic stem cells (HSPC) and progenitor cell (HSPC) engraftment procedure. Treatment in vivo of a HSPC donor with compounds that reduce PGE2 biosynthesis or PGE2 receptor antagonists alone, or in combination with other hematopoietic mobilization agents such as AMD3100 and G-CSF, increases the circulation of available HSPCs. Compounds that reduce the cellular synthesis of PGE2 include non-steroidal anti-inflammatory compounds such as indomethacin. Treatment ex vivo of HSPC with an effective amount of PGE2 or at least one of its derivatives such as 16,16-dimethyl prostaglandin E2 (dmPGE2), promotes HSPC engraftment. Similar methods may also be used to increase viral-mediated gene transduction efficacy into HSPC.

Abstract: The present invention relates to a method for preparing commercial scale quantities of human functional Betacells and to the establishment of cell lines. 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 Betacells, allowing to generate human Betacell lines. Such lines express little amount of insulin and have a gene expression profile that resembles to adult Betacells. In addition, the human Betacell lines are able to normalize glycemia of diabetic mice when transplanted, demonstrating their insulin secretion capabilities.