Abstract: The present invention relates to novel isolated antibodies, or the derivatives or antigen binding fragments of same, capable of binding to CXCR4 but also of inducing conformational changed of the CXCR4 homodimers and able to inhibit HIV-1 primary isolate replication in PBMC. More particularly, the present invention relates to the 515H7 and 301aE5 monoclonal antibodies, specific to the CXCR4 protein, as well as their use for the treatment of HIV infection. Pharmaceutical compositions comprising such antibodies and a process for the selection of such antibodies are also covered.

Abstract: Hypercellular nonhuman organisms have functionally inactivated expression of a cyclin inhibitor gene, especially p27. The growth rate of nonhuman organisms are increased such that a desired size is attained more quickly than as compared to nonvariant organisms. Inhibitors of the p27 cyclin dependent kinase inhibitor protein or sequences encoding the protein modulate vertebrate cell cycle progression and increase the proportion of dividing cells to non-dividing cells in a population of treated cells. As the proportion of dividing cells increases, the cell population, e.g., hematopoietic progenitor (stem) cells, is more efficiently used for gene therapy applications. Transgenic animals and plants, and knockout alleles are provided.

Abstract: The application describes a transgenic insect comprising a developmental stage-specific lethality system. The developmental stage-specific lethality system comprises a first gene expression cassette comprising a first promoter/enhancer element of a developmental stage-specific gene derived from an insect pest species, preferably from a member of the family Tephritidae, a first component of a transactivating system, a second gene expression cassette comprising a second component of the transactivating system, a second promoter responsive to the activity of the transactivating system, and a lethality inducing system. Also, the application describes a method of controlling reproduction in an insect population of interest, comprising providing a plurality of insects according to the invention and allowing the insects to interbreed with insects of the population of interest.

Abstract: The present invention is related to the discovery that serpina3n, a secreted protein, binds to and inhibits granzyme B activity. The invention thus provides cells that include a polynucleotide encoding a granzyme B inhibitory serpin, pharmaceutical compositions including a granzyme B inhibitory serpin or a polynucleotide encoding a granzyme B inhibitory serpin, methods for treating a patient in need of immunosuppression by administration of a granzyme B inhibitory serpin, and methods of transplanting cells (e.g., islet cells) expressing a granzyme B inhibitory serpin.

Abstract: It is an object of the present invention to provide a high affinity antibody effective as a diagnostic or therapeutic for various diseases; a transgenic mammal for producing the high affinity antibody; and a medicine comprising the high affinity antibody or a cell producing the high affinity antibody. According to the present invention, a transgenic mammal carrying a GANP gene transferred thereinto, its progeny, or a part thereof, and a method of producing a high affinity antibody using the same are provided.

Abstract: The present invention provides methods of altering gene expression of embryos to provide compositions and methods for efficient generation of transgenic animals. In particular, the present invention provides compositions and methods for generating germ-line transgenic animals by direct injection of nucleic acid molecules into animals.

Abstract: The present invention relates, generally, to a transgenic non-human animal model of hemophilia A, wherein the transgenic animal is deficient in endogenous Factor VIII and endogenous von Willebrand Factor, and methods to treat hereditary or acquired hemophilia A or von Willebrand Disease (VWD) by administration of exogenous human VWF.

Abstract: The present invention relates to mutant animals having a modified NMDA Receptor and use of the same for screening compounds useful for treating psychiatric and neurological disorders, such as schizophrenia, autism and Alzheimer's Disease. In particular, the invention provides an animal model that has mutation in phosphorylation of the NR1 subunit of the NMDAR, which causes behavioral deficits associated with psychiatric disorders useful for the evaluation of the therapeutic effects of psychotropic drugs for the treatment of these disorders.

Abstract: Double-stranded RNA (dsRNA) induces sequence-specific post-transcriptional gene silencing in many organisms by a process known as RNA interference (RNAi). Using a Drosophila in vitro system, we demonstrate that 19-23 nt short RNA fragments are the sequence-specific mediators of RNAi. The short interfering RNAs (siRNAs) are generated by an RNase III-like processing reaction from long dsRNA. Chemically synthesized siRNA duplexes with overhanging 3? ends mediate efficient target RNA cleavage in the lysate, and the cleavage site is located near the center of the region spanned by the guiding siRNA. Furthermore, we provide evidence that the direction of dsRNA processing determines whether sense or antisense target RNA can be cleaved by the produced siRNP complex.

Abstract: An object of the present invention is to provide a method which constantly enables organ regeneration for the purpose of achieving organ regeneration with higher efficiency. It has been discovered that, in a blastocyst complementation method, a next generation is born when a deficiency in an organ, such as pancreas and kidney, is complemented by injection of ES cells into a generated blastocyst, and further discovered that a transgenic animal having a pancreas or a kidney thus complemented can transmit the phenotype to the next generation as a founder. This discovery has revealed that organ regeneration can be accomplished by using such a founder. Thus, the present invention achieved the above-described object.

Abstract: The present invention relates to an in vitro method of diagnosing a drug-associated angioedema or a predisposition thereto in a subject being suspected to having developed or of having a predisposition to develop a drug-associated angioedema or in a subject being intended to be treated with a drug associated with the development of angioedema, the method comprising determining in a biological sample from said subject the presence or absence of a disease-associated mutation in a nucleic acid molecule regulating the expression of or encoding coagulation factor XII; wherein the presence of such a mutation is indicative of a drug-associated angioedema or a predisposition thereto.

Abstract: The present invention relates to a transgenic animal wherein DNA encoding p300 and a promoter exerting its activity in myocardial cells are introduced, and a screening method using the same.

Abstract: Isolated and purified MAR sequences of human and non-human animal origin are disclosed as are nucleotide sequences corresponding to or based on them. In particular, MARs and MAR constructs with high transcription and/or protein production enhancing activities are disclosed and so are methods for identifying such MARs, designing such MAR constructs and employing them, e.g., for high yield production of proteins.

Abstract: Disclosed herein are methods and compositions for gene targeting utilizing fusion molecules comprising a recombinase domain and a sequence-specific DNA-binding domain.

Abstract: The present invention relates to a DNA molecule comprising: (a) a first DNA sequence comprising: (aa) a coding sequence giving rise upon transcription to a factor that contributes to the reprogramming of a somatic cell into an induced pluripotent stem (iPS) cell; (ab) a promoter mediating the transcription of said coding sequence; and (ac) two sequence motifs that mediate excision of (aa) and/or (ab) from the DNA molecule, wherein one sequence motif is positioned 5? and the other sequence motif is positioned 3? of the sequence to be excised; (b) a second DNA sequence comprising a sequence motif that mediates site-specific integration of (a) into another DNA molecule.

Abstract: The invention provides methods and compositions for inducing brown fat cell differentiation through modulation of Prdm 16 activity or expression. Also provided are methods for preventing or treating obesity or an obesity related disorder in a subject through stimulation of Prdm 16 expression or activity. Further provided are methods for identifying compounds that are capable of modulating Prdm 16 expression or activity.

Abstract: The invention relates to mammalian PAI-I ligands and modulators. In particular, the invention relates to polypeptides, polypeptide compositions and polynucleotides that encode polypeptides that are ligands and/or modulators of PAI-I. The invention also relates to polyligands that are homopolyligands or heteropolyligands that modulate PAI-I activity. The invention also relates to ligands and polyligands localized to a region of a cell. The invention also relates to localization tethers and promoter sequences that can be used to provide spatial control of the PAI-I ligands and polyligands. The invention also relates to inducible gene switches that can be used to provide temporal control of the PAI-I ligands and polyligands. The invention also relates to methods of treating or preventing atherosclerosis. The invention also relates to methods of treating or preventing fibrosis.

Abstract: The present invention relates generally to tissue differentiation factor (TDF) analogs. More specifically, the invention relates to structure-based methods and compositions useful in designing, identifying, and producing molecules which act as functional modulators of TDF-like receptors. The invention further relates to methods of detecting, preventing, and treating TDF-associated disorders.

Abstract: A transgenic animal is provided. In certain embodiments, the transgenic animal comprises a genome comprising: an immunoglobulin light chain locus comprising: a) a functional immunoglobulin light chain gene comprising a transcribed variable region encoding: i. light chain CDR1, CDR2 and CDR3 regions that are composed of 2 to 5 different amino acids; and ii. a light chain framework; and, operably linked to the functional immunoglobulin light chain gene: b) a plurality of pseudogene light chain variable regions each encoding: i. light chain CDR1, CDR2 and CDR3 regions that are composed of the same 2 to 5 different amino acids as the CDRs of the functional gene; and ii. a light chain framework that is identical in amino acid sequence to the light chain framework of the transcribed variable region.

Abstract: The invention provides non-human transgenic animals as models of neurodegenerative brain pathology, including, but not limited to, Alzheimer's disease (AD), and cancer. The non-human transgenic animals of the present invention include an exogenous DNA that reduces or eliminates the expression and/or function of a molecular chaperone, including, but not limited to heat shock protein 110 (Hsp1 10) or heat shock protein 70 (Hsp70). These non-human transgenic animals may be used in methods of screening and identifying compounds useful for the prevention and/or treatment of neurodegenerative brain pathology and/or cancer.

Abstract: Compositions and methods for the identification, prognosis, classification, diagnosis, and treatment of leukemia or a genetic predisposition to leukemia are provided. The present invention is based on the discovery of a novel intragenic deletion in the v-ets erythroblastosis virus E26 oncogene homolog (ERG) allele which is shown herein to be associated with a novel subtype of B-progenitor acute lymphoblastic leukemia (ALL). In one embodiment, the intragenic deletion in ERG results in the expression of C-terminal domain deletion forms of the ERG polypeptide which lacks the DNA-binding PNT domain and CAE domain of the ERG polypeptide and have dominant negative ERG activity. In other embodiments, the intragenic deletions results in a loss of expression of the native ERG polypeptide.

Abstract: Disclosed herein are homozygously modified organisms and methods of making and using these organisms.

Abstract: The present invention provides certain animals, and in particular porcine animals, tissue and cells derived from these, which lack any expression of functional alpha 1,3 galactosyltransferase (?GT) and express one or more additional transgenes which make them suitable donors for pancreatic islet xenotransplantation. Methods of treatment and prevention of diabetes using cells derived from such animals are also provided.

Abstract: An I-MsoI homing endonuclease variant able to cleave mutant I-MsoI sites having variation at positions ±8 to ±10, a vector encoding said variant, a cell, an animal or a plant modified by said vector. Use of said I-MsoI endonuclease variant and derived products for genetic engineering, genome therapy and antiviral therapy.

Abstract: The present invention is directed to a Trypanosome-resistant, non-human transgenic animal whose somatic and germ cells comprise a nucleic acid which encodes an apolipoprotein L-I polypeptide (apoL-I). The apoL-I protein has the amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 4, and SEQ ID NO: 5. The first nucleic acid transgene is operatively associated with at least one expression regulatory sequence. Methods of producing and raising such transgenic animals as well as transgenic eggs and sperm are also disclosed.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences encoding immunodeficiency proteins. In particular, the animals or cells are generated using a zinc finger nuclease-mediated editing process. Also provided are methods of assessing the effects of agents in genetically modified animals and cells comprising edited chromosomal sequences encoding immunodeficiency proteins.

Abstract: The invention relates to compositions for the post-transcriptional inhibition of gene expression by means of the combined use of a modified U1 snRNA targeted at a pre-selected region in a target pre-mRNA and of a gene expression-silencing agent of the siRNA, shRNA and/or miRNA type, as well as the use of said combinations for the treatment of diseases caused by the unwanted over-expression of a protein.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences encoding proteins associated with ASD. In particular, the animals or cells are generated using a zinc finger nuclease-mediated editing process. Also provided are methods of using the genetically modified animals or cells disclosed herein to study ASD development and screen agents for assessing their effect on progression or symptoms of an ASD.

Abstract: The present invention provides a genetically modified silkworm or cell comprising at least one edited chromosomal sequence. In particular, the chromosomal sequence is edited using a zinc finger nuclease-mediated editing process. The disclosure also provides zinc finger nucleases that target specific chromosomal sequences in the silkworm genome.

Abstract: The present invention relates to a fusion protein comprising a Caspase domain or a functionally active variant thereof and a ligand binding domain of a nuclear hormone receptor, a nucleic acid coding for the fusion protein, a vector or cell comprising the nucleic acid, a method of producing the fusion protein, a non-human transgenic animal containing the nucleic acid, the use of the fusion protein for ligand-mediated induction of apoptosis of a cell, or for studying the function of a cell, tissue and/or organ or the use of a transgenic organism for studying the function of a cell at various developmental stages or as a disease model, a method for inducing apoptosis of a cell expressing a fusion protein or for identifying a ligand, or a medicament comprising a fusion protein, the nucleic acid, the vector or the cell, particularly for the treatment of cancer or for or after transplantation, particularly as safety mechanism.

Abstract: The present invention relates to a novel isolated antibody, or the derived compounds or functional fragments of same, capable of binding to CXCR4 but also of inducing conformational changed of the CXCR4 homodimers and/or heterodimers. More particularly, the present invention relates to the 414H5 and 515H7 antibodies, specific to the CXCR4 protein, as well as their use for the treatment of cancer. Pharmaceutical compositions composed of such antibodies and a process for the selection of such antibodies are also covered.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences associated with schizophrenia. In particular, the animals or cells are generated using a zinc finger nuclease-mediated editing process. The invention also provides zinc finger nucleases that target chromosomal sequence associated with schizophrenia and the nucleic acids encoding said zinc finger nucleases. Also provided are methods of assessing the effects of agents in genetically modified animals and cells comprising edited chromosomal sequences associated with schizophrenia.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences encoding ABC transporter proteins. In particular, the animals or cells are generated using a zinc finger nuclease-mediated editing process. Also provided are methods of assessing the effects of agents in genetically modified animals and cells comprising edited chromosomal sequences encoding ABC transporter proteins.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences encoding proteins associated with addiction disorders. In particular, the animals or cells are generated using a zinc finger nuclease-mediated editing process. The invention also provides zinc finger nucleases that target chromosomal sequence encoding addiction-related proteins and the nucleic acids encoding said zinc finger nucleases. Also provided are methods of using the genetically modified animals or cells disclosed herein to screen agents for addiction and withdrawal side effects and other effects.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences involved in tumor suppression. In particular, the animals or cells are generated using a zinc finger nuclease-mediated editing process. The invention also provides zinc finger nucleases that target chromosomal sequence involved in tumor suppression and the nucleic acids encoding the zinc finger nucleases. Also provided are methods of assessing the effects of agents in genetically modified animals and cells comprising edited chromosomal sequences involved in tumor suppression.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences encoding proteins associated with Parkinson's disease. In particular, the animals or cells are generated using a zinc finger nuclease-mediated editing process. Also provided are methods of using the genetically modified animals or cells disclosed herein to study PD development and screen agents for assessing their effect on progression or symptoms of PD.

Abstract: The invention relates to a DNA consisting of the nucleotide sequence shown in SEQ ID NO: 1, or a nucleotide sequence the same or substantially the same as a partial nucleotide sequence thereof containing at least one HRE consensus sequence, which transiently has a transcription promoting activity in a vascular endothelial cell-specific manner in a hypoxic state, or a vector containing a promoter containing the DNA, and the like. The prophylaxis and/or treatment, as well as diagnosis, of acute ischemic diseases are enabled by connecting a prophylactic and/or therapeutic gene or a reporter gene to the downstream of the vector and administering same to mammals.

Abstract: The present inventors produced transgenic silkworms which comprise a promoter of a DNA encoding a protein specifically expressed in the silk gland and a DNA encoding a recombinant antibody whose expression is regulated directly or indirectly by the promoter, and which secrete the recombinant antibody into the silk gland. The recombinant antibodies produced from the silk gland of the transgenic silkworms were confirmed to be active.

Abstract: This invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of a GCR gene. The invention also relates to a pharmaceutical composition comprising the dsRNA or nucleic acid molecules or vectors encoding the same together with a pharmaceutically acceptable carrier; methods for treating diseases caused by the expression of a GCR gene using said pharmaceutical composition; and methods for inhibiting the expression of GCR in a cell.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences encoding proteins that are associated with neurodevelopmental disorders. In particular, the animals or cells are generated using a zinc finger nuclease-mediated editing process. Also provided are methods of using the genetically modified animals or cells disclosed herein to screen agents for toxicity and other effects.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences encoding proteins that are associated with a secretase disorder. In particular, the animals or cells are generated using a zinc finger nuclease-mediated editing process. Also provided are methods of using the genetically modified animals or cells disclosed herein to screen agents for toxicity and other effects.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences encoding proteins that are associated with cognitive disorders. In particular, the animals or cells are generated using a zinc finger nuclease-mediated editing process. Also provided are methods of assessing the effects of agents in genetically modified animals and cells comprising edited chromosomal sequences associated with cognitive disorders.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences encoding proteins associated with AD. In particular, the animals or cells are generated using a zinc finger nuclease-mediated editing process. Also provided are methods of using the genetically modified animals or cells disclosed herein to study AD development and methods of assessing the effects of agents in genetically modified animals and cells comprising edited chromosomal sequences encoding proteins associated with AD.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal involved in cardiovascular disease. In particular, the animals or cells are generated using a zinc finger nuclease-mediated editing process. The invention also provides zinc finger nucleases that target chromosomal sequences involved in cardiovascular disease and the nucleic acids encoding said zinc finger nucleases. Also provided are methods of using the genetically modified animals or cells disclosed herein to screen agents for toxicity and other effects.

Abstract: Provided are methods for determining the susceptibility of an individual to a neuropsychiatric disorder, or a method of diagnosis or prognosis of the neuropsychiatric disorder (particularly schizophrenia) the methods comprising use of a pericentriolar material 1 (PCM1) marker which is located in the chromosomal region 8p21-22, for example a marker within the PCM1 gene locus or within 1000 kb of it. The invention also provides novel markers, and related materials and methods of detecting them, and identifying further molecules for use in therapy and diagnosis.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences encoding proteins that are associated with trinucleotide repeat expansion disorders. In particular, the animals or cells are generated using a zinc finger nuclease-mediated editing process. Also provided are methods of using the genetically modified animals or cells disclosed herein to screen agents for toxicity and other effects.

Abstract: The invention relates to enzymes having xylanase, mannanase and/or glucanase activity, e.g., catalyzing hydrolysis of internal ?-1,4-xylosidic linkages or endo-?-1,4-glucanase linkages; and/or degrading a linear polysaccharide beta-1,4-xylan into xylose. Thus, the invention provides methods and processes for breaking down hemicellulose, which is a major component of the cell wall of plants, including methods and processes for hydrolyzing hemicelluloses in any plant or wood or wood product, wood waste, paper pulp, paper product or paper waste or byproduct. In addition, methods of designing new xylanases, mannanases and/or glucanases and methods of use thereof are also provided. The xylanases, mannanases and/or glucanases have increased activity and stability at increased pH and temperature.

Abstract: The present invention relates to the use of regulatory sequences for mediating specific, early transient expression in proliverative neuronal determined cells. Furthermore, the uses of recombinant nucleic acid molecules comprising said defined regulatory sequences for mediating specific, early transient expression in proliverative neuronal determined cells as well as for the generation of non-human transgenic organisms and/or host cells are disclosed. In addition, the invention provides for transgenic non-human animals and/or host cells comprising said regulatory sequences and/or recombinant nucleic acid molecules. The invention also describes methods for the preparation of such vectors, host cells and transgenic non-human animals as well as methods for the detection and/or isolation of neuronal determined cells.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences encoding proteins that are associated with nociception or taste disorders. In particular, the animals or cells are generated using a zinc finger nuclease-mediated editing process. Also provided are methods of using the genetically modified animals or cells disclosed herein to screen agents for toxicity and other effects.

Abstract: The present invention provides genetically modified animals and cells comprising edited chromosomal sequences encoding proteins that are associated with neurotransmission disorders. In particular, the animals or cells are generated using a zinc finger nuclease-mediated editing process. Also provided are methods of using the genetically modified animals or cells disclosed herein to screen agents for toxicity and other effects.