Abstract: This invention relates to compositions and methods of delivering therapeutic agents to bone. More specifically, the invention relates to endowing a large molecule vectors i.e., adeno virus, retrovirus, liposomes, micelles, natural and synthetic polymers, or combinations thereof, with the ability to target bone tissue in vivo and with improved stability in the blood, by attaching multiple copies of acid amino acid peptides. One preferred embodiment of the invention relates to endowing an adeno-associated virus (AAV) vector with the ability to target bone-tissue in vivo and improve its stability, by the addition of multiple acidic amino acid peptides attached to the capsid of the viral vector.

Abstract: The present invention provides new uses of recombinant adenoviral vectors in vaccination regimens, such as prime/boost set-ups and subsequent vaccinations and applications for gene therapy. Moreover, the invention provides new assays to determine the best regimen for applying the most suitable recombinant viral vector in a vaccination or gene therapy setting.

Abstract: Sequences are provided that are capable of directing circular adeno-associated virus replication, useful in vectors for providing therapeutic agents to a subject in need thereof. The vectors of the invention are particularly useful in the treatment of acute medical conditions requiring rapid gene expression. Further provided are methods for producing packaged defective viral 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: The present invention includes compositions and methods for regenerating glucose-responsive cells by ultrasound-targeted microbubble destruction in the pancreas, wherein the composition comprises a pre-assembled liposome-nucleic acid complex in contact with in and about a microbubble, wherein the pre-assembled liposome-nucleic acid complex comprises a NeuroD gene under the control of the promoter, wherein disruption of the microbubble in the pancreas at a target site delivers the nucleic acid into pancreas cells at the location of the ultrasound disruption, wherein cells that incorporate the nucleic acid express insulin in response to high blood glucose levels.

Abstract: Methods are provided for inducing non-pluripotent cells to become pluripotent. Methods also include identifying and isolating induced pluripotent (iPS) cells and uses thereof. Compositions and kits for carrying out the subject methods are also provided.

Abstract: Described is a replication competent recombinant virus, being capable to replicate and having lytic capacity in target cells, the said cell being hampered in the p53 dependent apoptosis pathway, the virus including in the genome thereof, the coding sequence of at least one restoring factor functional in restoring the p53 apoptosis pathway in the said target cells, operably linked to one or more expression control sequences, functional in the said target cells, as well as the use thereof in the preparation of a medicament, in particular for suppressing uncontrolled cell growth.

Abstract: Provided are methods and means to increase the stability and/or the packaging capacity of recombinant adenoviruses, by overexpression of pIX in an adenoviral packaging cell, by retaining at least a part of the E1B-55K region in the recombinant adenoviral vector or by regulating pIX with a heterologous promoter. The invention further relates to methods and means for the production of such adenoviruses on complementing cell lines, wherein the early region 4 open reading frame 6 (E4-orf6) encoding nucleic acid is present in the adenovirus and wherein the E4-orf6 gene product is compatible with one or more products of the E1 gene products in the complementing cell, such that the adenoviral vector can be efficiently produced by the complementing cell.

Abstract: This invention relates to compositions and methods for selective expression of a heterologous nucleic acid sequence in a targeted tissue, and more particularly to the glucose regulated protein 78 (grp78) stress-responsive promoter and its use in gene therapy and the production of transgenic animals.

Abstract: The present invention provides a drug capable of causing cancer cells to restore anticancer drug sensitivity in cases in which cancer has acquired resistance to an anticancer drug and inducing cell death in cancer cells. The present invention specifically provides a cancer cell death inducing agent comprising REIC/Dkk-3 DNA as an active ingredient and having effects of potentiating an anticancer drug for cancer cells having anticancer drug resistance.

Abstract: The invention provides methods of culturing mammalian taste cells, including taste receptor cells. Cells are maintained for a duration of up to three months and longer while maintaining molecular and functional characteristics of mature taste cells. The cells are cultured on coated cell culture vessels and, from first replacement of medium onwards, the medium is replaced in intervals of at least 5 days. The invention further provides isolation and culturing methods of taste cells wherein the time that the cells are exposed to isolation solution and proteolytic enzymes is minimized and the cells are cultured in coated culture vessels with the medium replaced in intervals of at least 5 days from first replacement onwards. The invention further provides cultured taste cells, transfection and assay methods, and taste cell assay buffers with an osmolarity of about 300-320 and pH of about 7.0-7.3.

Abstract: Methods for inhibiting retinal cell death by altering expression of one or more of HDAC4, HDAC5, HDAC6, HDAC7, and HIF1? in a retinal cell are provided.

Abstract: Isolated polypeptides, isolated polynucleotides or expression vectors encoding same, viral display vehicles which can be specifically bind an exposed epitope shared by mutant, but not wild type, p53 protein are provided. Also provided are methods of inducing apoptosis and treating cancer as well as diagnosing a p53-related cancer using the isolated polypeptides uncovered by the present invention.

Abstract: Adeno-associated virus 7 sequences, vectors containing same, and methods of use are provided.

Abstract: The invention provides adenovirus and retrovirus vectors useful to prepare influenza virus. Also provided is a canine RNA polymerase I promoter and vectors having that promoter.

Abstract: A polypeptide comprising a preS1 region of hepatitis B virus (HBV), or a fragment thereof, and/or the preS2 region of HBV or a fragment thereof, and methods of use to inhibit virus infection are disclosed. A lentivirus comprising hepatitis B virus (HBV) envelope proteins, or a fragment thereof, and/or the L envelope protein of HBV and/or the M envelope protein of HBV or a fragment thereof, and/or the S envelope protein of HBV or a fragment thereof, and methods of use of this lentivirus HBV pseudovirus as a gene therapy to target hepatocytes for the administration of therapeutic agents are also disclosed.

Abstract: The present invention relates to recombinant DNA molecules such as plasmids, non-viral vectors, viral vectors and hybrids thereof, and more particularly to vector modifications that improve expression of said DNA molecules in cell lines and organisms.

Abstract: The invention relates to recombinant VSV viruses and viral vectors which produce a glycoprotein GP of the lymphocyte choriomeningitis virus (LCMV) instead of the G protein of the VSV, to virus producing cells which produce LCMV-GP-pseudotyped VSV virions, and to the use of said vectors and cells in the therapy of solid tumors, especially brain tumors.

Abstract: This invention provides a new approach to the design of a virus with a defective replication cycle, which can be rescued by wild type virus co-infection, and which expresses foreign antigenic epitopes that contribute to the elimination of virus infected cells and then to viral clearance. The vector of the invention, by expression of epitopes derived from common pathogens, by-passes existing tolerance of virus specific T cell responses. The vector will only replicate in virus infected cells.

Abstract: The presently disclosed subject matter provides methods of inhibiting a host innate response to activator-mediated proliferative signals in a primary B cell. In some embodiments a method is provided for immortalized primary B cells. In some embodiments a method is provided for increasing efficiency of EBV transformation of primary B cells. In some embodiments a method is provided for increasing proliferation of primary B cells in culture. In some embodiments a method is provided for producing a monoclonal antibody. In some embodiments a method is provided for identifying a novel broadly neutralizing antibody having a desired antigen specificity. Also provided are antibodies produced according the methods of the presently disclosed subject matter.

Abstract: The present invention relates to supports for bioassays and the use thereof in cell culturing and in cell-based methods and assays. More precisely, the invention provides solid materials coated with films of nanostructured titanium dioxide suitable for the immobilisation of viruses and for cell-adhesion. The nanostructured TiO2 film-coated support of the invention is particularly useful for the preparation of microarrays for genetic and phenotypic analysis.

Abstract: The invention includes a composition comprising a recombinant adeno-associated viral vector comprising at least two adeno-associated virus inverted terminal repeats, a promoter/regulatory sequence, isolated DNA encoding Factor IX and accompanying 5? and 3? untranslated regions and a transcription termination.

Abstract: The invention relates to recombinant vectors for inducible and/or tissue specific expression of double-stranded RNA molecules that interfere with the expression of a target gene. In certain embodiments, the invention relates to the use of Tet (tetracycline)-responsive RNA Polymerase II (Pol II) promoters (e.g., TetON or TetOFF) to direct inducible knockdown in certain cells of an integrated or an endogenous gene, such as p53. The invention also relates to a method for producing transgenic animals (e.g., mice) expressing inducible (such as tetracycline-regulated), reversible, and/or tissue-specific double-stranded RNA molecules that interfere with the expression of a target gene.

Abstract: The present invention is directed to a system to significantly increase the expression of genes of interest, and in particular proteins and polypeptide products. Expression of hantavirus nucleocapsid protein (N) by itself results in augmented translational expression of diverse genes. The mechanism of this augmentation relies on the ability of N to replace the cellular cap binding complex to attain more efficient translation initiation—the result being great mRNA production and greater protein/polypeptide production. The inventors have also recently found that inclusion of a 5? untranslated leader region (viral UTR) from a viral RNA, in conjunction with N, leads to even more robust expression. This mechanism appears to involve recognition of the viral UTR by the N to provide even more robust protein production.

Abstract: A recombinant varicella-zoster virus; a process for producing the same; a pharmacological composition containing recombinant varicella-zoster virus; a vector containing a genomic gene of varicella-zoster virus and BAC vector sequence; cells containing the above vector; a fragment capable of homologous recombination with a genome of varicella-zoster virus; and a nucleic acid cassette containing the BAC vector sequence. For these, there is provided a process for producing recombinant varicella-zoster virus, comprising use of the BAC vector sequence.

Abstract: The present invention is concerned with means and methods for producing adenovirus particles comprising a chimeric adenovirus spike protein that essentially lacks a functional knob domain. One aspect of the invention is concerned with a method for producing adenovirus particles comprising providing cells that are permissive for adenovirus replication with an adenovirus vector, with nucleic acid encoding said chimeric adenovirus spike protein and with nucleic acid encoding at least one adenovirus E3 region protein or a functional part, derivative and/or analogue thereof, said method further comprising culturing said permissive cells to allow for at least one replication cycle of said adenovirus virus and harvesting said adenovirus particle.

Abstract: The present invention relates to the use of Yersinia outer protein M (YopM), a YopM fragment, or a YopM variant, which is capable of autopenetrating the cell membrane and of integrating into the cell cytosol without the requirement of additional factors for delivering a cargo molecule across the membrane to the cytosol of a cell. The present invention also relates to a pharmaceutical composition comprising YopM, a YopM fragment, or a YopM variant being capable of autopenetrating the cell membrane and of integrating into the cell cytosol without the requirement of additional factors for the regulation of inflammatory reactions of the immune system and the treatment of diseases caused by autoimmunity of the host. The present invention further relates to a YopM fragment or variant, which is capable of autopenetrating the cell membrane and of integrating into the cell cytosol without the requirements of additional factors as well as such proteins or YopM linked to a cargo molecule.

Abstract: The present invention provides an attenuated virus, which is derived from Modified Vaccinia Ankara virus, wherein the MVA-BN virus, or a derivative thereof, induces at least substantially the same level of immunity in vaccinia virus prime/vaccina virus boost regimes when compared to DNA prime/vaccinia virus boost regimes. It further describes recombinant viruses derived from this virus and the use of the virus, or its recombinants, as a medicament or vaccine. A method is provided for inducing an immune response in individuals who may be immune-compromised, receiving antiviral therapy, or have a pre-existing immunity to the vaccine virus.

Abstract: The current invention provides for methods and medicaments that apply an oligonucleotide comprising aninosine and/or an uracile and/or a nucleotide containing a base able to form a wobble base pair, said oligonucleotide being preferably RNAse H substantially independent and being complementary only to a repetitive sequence in a human gene transcript, for the manufacture of a medicament for the diagnosis, treatment or prevention of a cis-element repeat instability associated genetic disorders in humans. The invention hence provides a method of treatment for cis-element repeat instability associated genetic disorders. The invention also pertains to a modified oligonucleotide which can be applied in a method of the invention to prevent the accumulation and/or translation of repeat expanded transcripts in cells.

Abstract: The invention relates to a method for the transfer of molecular substances, for example proteins or nucleic acids in cells, in the case of using DNA combined with a possible gene expression. A prokaryotic nucleic acid-binding protein is used for the transfer, which is preferably obtained from a thermostable organism. Where the substance to be transferred is a nucleic acid, the protein forms a reversible complex with the nucleic acid. The prokaryotic protein condenses and compacts the nucleic acids. Said nucleic acids can be taken up in the target cells after suitable incubation.

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: The invention is directed to a chimeric gammaretrovirus comprising an gammaretroviral virion which contains a lentiviral Vpx protein and methods of use thereof.

Abstract: This invention provides methods for obtaining targeted gene modification in vertebrate cells using parvoviral vectors, including adeno-associated virus (AAV). The parvoviral vectors used in the methods of the invention are capable of targeting a specific genetic modification to a preselected target locus in a cellular genome by homologous pairing.

Abstract: A method for preparing a ?? T cell population, characterized in that the method includes the step of culturing a cell population containing ?? T cells, in the presence of (a) fibronectin, a fibronectin fragment or a mixture thereof and (b) an activating factor of ?? T cells. According to the present invention, a method for preparing a ?? T cell population is provided. The ?? T cell population obtained by the method is suitably used in, for example, immunotherapy. Therefore, the method of the present invention is expected to greatly contribute to a medical field.

Abstract: The present invention provides a screening method for somatic cell nuclear reprogramming substances, which comprises (a) a step for bringing into contact with each other a somatic cell comprising a gene wherein a marker gene is present at a position permitting expression control by the expression control region of an ECAT gene, and a test substance, and (b) a step following the aforementioned step (a), for determining the presence or absence of the emergence of cells expressing the marker gene, and selecting a test substance allowing the emergence of the cells as a somatic cell nuclear reprogramming substance candidate, and the like.

Abstract: The invention relates to the field of influenza vaccine production. Influenza vaccines have been produced in embryonated hens' eggs for over 50 years, but recently there have been considerable efforts to develop cell culture systems for vaccine production. The invention provides a nucleic acid comprising an influenza gene segment and a bacteriophage polymerase promotor or a complementary strand of said nucleic acid, and a cell comprising such a nucleic acid capable of producing desired influenza virus. Furthermore, the invention provides a composition comprising a cell or material derived from a cell according to the invention and a virus or material derived from a viral particle according to the invention.

Abstract: Disclosed is a method for manufacturing stem cells including preparing Oct-4 gene, Sox2 gene, C-myc gene, and Klf-4 gene from mouse embryonic stem cells, and allowing each of the genes to be infected in host cells using a lentiviral vector system to generate viruses in which each of the genes are induced; concentrating or mixing each of the viruses to prepare a virus concentrated mixture, and mixing the virus concentrated mixture and a first culture solution to prepare a virus solution; floating mouse somatic cells having been cultivated in advance in a first culture dish, and mixing and reacting the floated somatic cells and the virus solution to prepare a somatic cell-virus mixture; adding and retaining the somatic cell-virus mixture as is in a second culture dish including a second culture solution to induce the genes in the somatic cells; and cultivating the somatic cells.

Abstract: The present invention relates to the identification of a gene, now designated negevin (ngvn), that is involved in the genetic disease Bardet Biedl Syndrome (BBS), which is characterized by such diverse symptoms as obesity, diabetes, hypertension, mental retardation, renal cancer and other abnormalities, retinopathy and hypogonadism. The human NGVN protein disclosed herein is 731 amino acids in length and is coded for by a gene spanning 17 exons. Homologs have been identified in mouse, rat, zebrafish. Methods of use for the gene, for example in diagnosis and therapy of BBS and in drug screening, also are described.

Abstract: The present invention generally provides methods for administering a composition having an ILK-based protein or peptide having a sequence that is at least 90% homologous to wild-type human integrin-linked kinase (ILK) protein for use in treating or administering to cardiac cells in vitro or in vivo. The ILK-based protein or peptide may further have a mutation or substitution at a position corresponding to amino acid position 211 of wild-type human ILK replacing the arginine (R) with an alanine (A). The present invention further provides compositions having polynucleotides encoding such proteins or peptides. Various vectors, delivery reagents and the like are also provided for use in delivering the compositions to cells. The compositions administered to cells in vitro or in vivo according to present methods may be used to treat, prevent, etc., heart failure, ischemic disease, cardiomyopathy, etc.

Abstract: Viral-based vectors are genetically engineered to express inhibitors of the anti-viral immune system (e.g. inhibitors of the type I interferon response) in order to enhance transgene expression. The transgenes may encode antigens or other therapeutic agents.

Abstract: The present invention provides a modified cell having adhesion properties that are increased as compared to the adhesion properties of an unmodified cell, comprising a) a recombinant nucleic acid encoding an integrin ?3 subunit; b) a recombinant nucleic acid encoding an integrin ?v subunit; c) a recombinant nucleic acid encoding an integrin ?IIb subunit; and/or d) any combination of (a), (b) and (c).

Abstract: The present invention provides methods of achieving directed evolution of viruses by in vivo screening or “panning” to identify viruses comprising scrambled AAV capsids having characteristics of interest, e.g., tropism profile and/or neutralization profile (e.g., ability to evade neutralizing antibodies). The invention also provides scrambled AAV capsids and virus particles comprising the same.

Abstract: The present invention provides methods to produce pluripotent stem cells from adult cells. In particular, the present invention provides methods to produce pluripotent stem cells from somatic cells without the use of a feeder-cell layer or an agent that increases efficiency of retroviral transfection.

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 disclosure provides a method for culturing cells in exogenous lactic acid. Certain aspects of the present disclosure include the production of recombinant proteins, such as antibodies and fragments thereof. Certain aspects of the present disclosure also relate to methods of controlling lactic acid production, pH stability and osmolality in cell culture.

Abstract: The present invention refers to the construction of cloning vectors containing the max gene. Especially, the present invention refers to the introduction of cloning vectors containing the max gene in cells using transport vectors. In addition, the presence of cloning vectors containing the max gene in cells allows the differential expression of the max gene in the same cells. In addition, the present invention refers to a method of gene therapy in which the differential expression of the max gene has cytoprotective activity, especially neuroprotective activity, and is capable of application to medical and veterinary therapeutics of neurodegenerative conditions.

Abstract: Methods of expressing LIM mineralization protein in non-osseous mammalian cells, such as stem cells or intervertebral disc cells (e.g., cells of the annulus fibrosus, or cells of the nucleus pulposus) are described. The methods involve transfecting the cells with an isolated nucleic acid comprising a nucleotide sequence encoding a LIM mineralization protein operably linked to a promoter. Transfection may be accomplished ex vivo or in vivo by direct injection of virus or naked DNA, or by a nonviral vector such as a plasmid. Expression of the LIM mineralization protein can stimulate proteoglycan and/or collagen production in cells capable of producing proteoglycyan and/or collagen. Methods for treating disc disease associated with trauma or disc degeneration are also described.

Abstract: The disclosure relates to a method of reprogramming one or more somatic cells, e.g., partially differentiated or fully/terminally differentiated somatic cells, to a less differentiated state, e.g., a pluripotent or multipotent state. In further embodiments the invention also relates to reprogrammed somatic cells produced by methods of the invention, to uses of said cells, and to methods for identifying agents useful for reprogramming somatic cells.

Abstract: The invention concerns a vaccine that can induce protection against disease especially in consequence of a lentivirus infection, especially an infection with the Feline Leukosis virus. Such vaccine comprises codon-optimized DNA sequences encoding structural proteins and the most important membrane protein of FeLV.

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.