Method Of Making A Transgenic Nonhuman Animal Patents (Class 800/21)
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Patent number: 8952215Abstract: 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.Type: GrantFiled: October 18, 2006Date of Patent: February 10, 2015Assignees: Nitto Boseki Co., Ltd., National Institute of Agrobiological SciencesInventors: Toshiki Tamura, Isao Kobayashi, Toshio Kanda, Keiro Uchino, Katsuhiro Katayama, Tatsuya Ohashi, Iwao Kiyokawa, Hisae Arai, Noriyuki Funahashi
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Publication number: 20150040253Abstract: The invention provides genetically modified non-human animals that express a humanized MHC II protein (humanized MHC II ? and ? polypeptides), as well as embryos, cells, and tissues comprising the same. Also provided are constructs for making said genetically modified animals and methods of making the same. Methods of using the genetically modified animals to study various aspects of human immune system are provided.Type: ApplicationFiled: August 8, 2014Publication date: February 5, 2015Inventors: Lynn Macdonald, Andrew J. Murphy, Naxin Tu, Cagan Gurer, Vera Voronina, Sean Stevens
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Publication number: 20150040254Abstract: Provided is a porcine CD28 receptor molecule, which is: 1) a protein consisting of an amino acid sequence represented by SEQ ID NO:2, or 2) a protein derived from 1) by substitution, deletion or addition of one or several amino acids in the amino acid sequence represented by SEQ ID NO:2 and having equivalent activity with 1). Further provided is a gene for coding the porcine CD28 receptor, the nucleotide sequence of which is shown as SEQ ID NO:1. When the provided co-stimulating receptor CD28 is expressed specifically and highly in a T cell, the activation, proliferation and cell factor secretion activity of the T cell when stimulated by an antigen can be enhanced, thereby enhancing the acquired immune response of a host and enhancing the immune effect of a vaccine. FIG. 8 is selected as the drawing attached to the Abstract.Type: ApplicationFiled: December 19, 2011Publication date: February 5, 2015Applicant: CHINA AGRICULTURAL UNIVERSITYInventors: Xun Suo, Xianyong Liu, Huali Su, Xinxin Zhao, Xiaoxi Huang
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Patent number: 8946505Abstract: Targeting constructs and methods of using them are provided for differentiation-dependent modification of nucleic acid sequences in cells and in non-human animals. Targeting constructs comprising a promoter operably linked to a recombinase are provided, wherein the promoter drives transcription of the recombinase in an differentiated cell but not an undifferentiated cell. Promoters include Blimp1, Prm1, Gata6, Gata4, Igf2, Lhx2, Lhx5, and Pax3. Targeting constructs with a cassette flanked on both sides by recombinase sites can be removed using a recombinase gene operably linked to a 3?-UTR that comprises a recognition site for an miRNA that is transcribed in undifferentiated cells but not in differentiated cells. The constructs may be included in targeting vectors, and can be used to automatically modify or excise a selection cassette from an ES cell, a non-human embryo, or a non-human animal.Type: GrantFiled: July 3, 2013Date of Patent: February 3, 2015Assignee: Regeneron Pharmaceuticals, Inc.Inventors: David Frendewey, Guochun Gong, Ka-Man Venus Lai, David M. Valenzuela
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Patent number: 8946504Abstract: Targeting constructs and methods of using them are provided for differentiation-dependent modification of nucleic acid sequences in cells and in non-human animals. Targeting constructs comprising a promoter operably linked to a recombinase are provided, wherein the promoter drives transcription of the recombinase in an differentiated cell but not an undifferentiated cell. Promoters include Blimp1, Prm1, Gata6, Gata4, Igf2, Lhx2, Lhx5, and Pax3. Targeting constructs with a cassette flanked on both sides by recombinase sites can be removed using a recombinase gene operably linked to a 3?-UTR that comprises a recognition site for an miRNA that is transcribed in undifferentiated cells but not in differentiated cells. The constructs may be included in targeting vectors, and can be used to automatically modify or excise a selection cassette from an ES cell, a non-human embryo, or a non-human animal.Type: GrantFiled: July 3, 2013Date of Patent: February 3, 2015Assignee: Regeneron Pharmaceuticals, Inc.Inventors: David Frendewey, Guochun Gong, Ka-Man Venus Lai, David M. Valenzuela
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Publication number: 20150033372Abstract: The present invention relates inter alia to improvements in the production of chimaeric antibodies in non-human transgenic vertebrates such as mice and rats bearing one or more chimaeric antibody transgenes. In particular, the invention provides for improved non-human vertebrates and cells in which VpreB has been species-matched with the variable region of the chimaeric antibodies. Also, embodiments also provide for species-matching of the entire surrogate light chain for efficient pairing with chimaeric heavy chains during B-cell development in vivo in a non-human transgenic vertebrate setting.Type: ApplicationFiled: March 26, 2014Publication date: January 29, 2015Applicant: Kymab LimitedInventors: Allan Bradley, E-Chiang Lee, Qi Liang, Dominik Spensberger, Nicholas England
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Publication number: 20150026831Abstract: This invention relates transgenic animals that overexpress TL1A in a tissue specific manner to model inflammatory bowel disease (IBD), such as colitis, Crohn's disease and ulcerative colitis, fibrosis, and related inflammatory diseases and conditions. TL1A transgenic animals constitutively express both TL1A and GFP in lymphoid and myeloid cell lineages, allowing convenient identification and sorting of immune cells involved in IBD disease progression, such as T-cells, antigen presenting cells (APC), and dendritic cells (DC). TL1A transgenic animals may be induced to exhibit gross fibrosis, or isolated cells may be implanted into immunodeficient mice to establish colitis.Type: ApplicationFiled: May 8, 2014Publication date: January 22, 2015Applicant: CEDARS-SINAI MEDICAL CENTERInventors: David Q. Shih, Stephan R. Targan
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Publication number: 20150020223Abstract: The invention provides for delivery, engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are delivery systems and tissues or organ which are targeted as sites for delivery. Also provided are vectors and vector systems some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells to ensure enhanced specificity for target recognition and avoidance of toxicity and to edit or modify a target site in a genomic locus of interest to alter or improve the status of a disease or a condition.Type: ApplicationFiled: September 9, 2014Publication date: January 15, 2015Inventors: Feng Zhang, Randall Jeffrey Platt, Guoping Feng, Yang Zhou
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Publication number: 20150020224Abstract: Non-human animals, e.g., mammals, e.g., mice or rats, are provided comprising an immunoglobulin heavy chain locus that comprises a rearranged human immunoglobulin heavy chain variable region nucleotide sequence. The rearranged human immunoglobulin heavy chain variable region nucleotide sequence may be operably linked to a heavy or light chain constant region nucleic acid sequence. Also described are genetically modified non-human animals comprising an immunoglobulin light chain locus comprising one or more but less than the wild type number of human immunoglobulin light chain variable region gene segments, which may be operably linked to a light chain constant region nucleic acid sequence. Also provided are methods for obtaining nucleic acid sequences that encode immunoglobulin light chain variable domains capable of binding an antigen in the absence of a heavy chain.Type: ApplicationFiled: September 26, 2014Publication date: January 15, 2015Applicant: Regeneron Pharmaceuticals, Inc.Inventors: John McWhirter, Cagan Gurer, Karolina A. Meagher, Lynn Macdonald, Andrew J. Murphy
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Patent number: 8933203Abstract: A method of using vaults as carrier molecules to deliver one or more than one substance to an organism, or to a specific tissue or to specific cells, or to an environmental medium. A vault-like particle. A method of preventing damage by one or more than one substance to an organism, to a specific tissue, to specific cells, or to an environmental medium, by sequestering the one or more than one substance within a vault-like particle. A method of delivering one or more than one substance or a sensor to an organism, to a specific tissue, to specific cells, or to an environmental medium. According to another embodiment of the present invention, there is provided a method of making vault-like particles, and making vault-like particles comprising one or more than one substance, or one or more than one sensor.Type: GrantFiled: October 15, 2008Date of Patent: January 13, 2015Assignee: The Regents of the University of CaliforniaInventors: Leonard H. Rome, Valerie A. Kickhoefer, Raval-Fernandes Sujna, Phoebe L. Stewart
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Publication number: 20150013023Abstract: Mice that comprise a replacement of endogenous mouse IL-6 and/or IL-6 receptor genes are described, and methods for making and using the mice. Mice comprising a replacement at an endogenous IL-6R? locus of mouse ectodomain-encoding sequence with human ectodomain-encoding sequence is provided. Mice comprising a human IL-6 gene under control of mouse IL-6 regulatory elements is also provided, including mice that have a replacement of mouse IL-6-encoding sequence with human IL-6-encoding sequence at an endogenous mouse IL-6 locus.Type: ApplicationFiled: September 19, 2014Publication date: January 8, 2015Applicant: REGENERON PHARMACEUTICALS, INC.Inventors: Li-Hsien Wang, Anthony T. Dore, JR., Sean Stevens, Andrew J. Murphy
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Publication number: 20150013022Abstract: Mice that comprise a replacement of endogenous mouse IL-6 and/or IL-6 receptor genes are described, and methods for making and using the mice. Mice comprising a replacement at an endogenous IL-6R? locus of mouse ectodomain-encoding sequence with human ectodomain-encoding sequence is provided. Mice comprising a human IL-6 gene under control of mouse IL-6 regulatory elements is also provided, including mice that have a replacement of mouse IL-6-encoding sequence with human IL-6-encoding sequence at an endogenous mouse IL-6 locus.Type: ApplicationFiled: September 19, 2014Publication date: January 8, 2015Applicant: REGENERON PHARMACEUTICALS, INC.Inventors: Li-Hsien Wang, Anthony T. Dore, JR., Sean Stevens, Andrew J. Murphy
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Patent number: 8921643Abstract: Disclosed are a method for acquiring a germ line chimeric fish having fish haploid germ cells, a germ line chimeric fish having haploid germ cells obtained by the aforesaid method, and a genetically identical gamete, said gamete having been derived from a donor haploid germ cell, produced by a germ line chimeric fish obtained by the aforesaid method.Type: GrantFiled: February 9, 2011Date of Patent: December 30, 2014Assignee: National University Corporation Hokkaido UniversityInventors: Etsuro Yamaha, Katsutoshi Arai, Takafumi Fujimoto, Taiju Saito
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Patent number: 8921642Abstract: Described are transgenic animals for conditional and inducible cell targeting, that express a dimerizable conditional-STOP caspase 3 transgene.Type: GrantFiled: January 12, 2009Date of Patent: December 30, 2014Assignee: Massachusetts Eye and Ear InfirmaryInventors: Albert Edge, Masato Fujioka
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Patent number: 8916743Abstract: Provided is a method of assessing a potential for development of Dravet syndrome with high accuracy, and use thereof. The method according to the present invention of assessing a potential for development of Dravet syndrome includes, with use of a sample taken from a subject, detecting whether or not a mutation is on ?-subunit type 1 of voltage-gated sodium ion channel NaV1.1, and detecting whether or not a mutation is on ?-subunit type 1 of voltage-gated calcium ion channel CaV2.1.Type: GrantFiled: June 23, 2014Date of Patent: December 23, 2014Assignee: National University Corporation Okayama UniversityInventors: Iori Ohmori, Mamoru Ouchida
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Patent number: 8907157Abstract: The invention provides methods for the production of transgenic animals comprising a recombinant Ig locus, as well as transgenic antibodies derived therefrom. The methods involve meganuclease cleavage-stimulated homologous recombination in mammalian embryos.Type: GrantFiled: February 5, 2010Date of Patent: December 9, 2014Assignee: OMT, Inc.Inventor: Roland Buelow
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Publication number: 20140359799Abstract: An in vitro method of producing a mouse cell having a genetic modification at a preselected genomic target locus includes transducing into the mouse cell an effective amount of a hybrid recombinant adeno-associated virus (AAV) vector that includes an AAV targeting construct of a first serotype packaged with a variant AAV capsid protein different than a capsid protein of the first serotype.Type: ApplicationFiled: December 24, 2012Publication date: December 4, 2014Inventors: Zhengne Wang, Xiujing Feng, Peng Zhang, Yujun Hao
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Publication number: 20140359797Abstract: The present invention relates inter alia to improvements in the production of chimaeric antibodies in non-human transgenic vertebrates such as mice and rats bearing one or more chimaeric antibody transgenes. In particular, the invention provides for improved non-human vertebrates and cells in which VpreB has been species-matched with the variable region of the chimaeric antibodies. Also, embodiments also provide for species-matching of the entire surrogate light chain for efficient pairing with chimaeric heavy chains during B-cell development in vivo in a non-human transgenic vertebrate setting.Type: ApplicationFiled: March 26, 2014Publication date: December 4, 2014Applicant: Kymab LimitedInventors: Allan Bradley, E-Chiang Lee, Qi Liang, Dominik Spensberger, Nicholas England
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Publication number: 20140351966Abstract: The present invention relates to a new method of gene integration in cells comprising the steps of: preparation of a suspension of poly nucleotide fragments comprising the desired gene in a hypotonic solution; administration of said suspension to cells or tissues; and maintenance of the cells or tissues in vitro or in its normal physiological condition. The invention also relates to a method of generating transgenic animal.Type: ApplicationFiled: December 4, 2013Publication date: November 27, 2014Applicant: National Institute of ImmunologyInventors: Subeer Suhash Majumdar, Abul Usmani, Nirmalya Ganguli
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Patent number: 8895802Abstract: A method for engineering and utilizing large DNA vectors to target, via homologous recombination, and modify, in any desirable fashion, endogenous genes and chromosomal loci in eukaryotic cells. These large DNA targeting vectors for eukaryotic cells, termed LTVECs, are derived from fragments of cloned genomic DNA larger than those typically used by other approaches intended to perform homologous targeting in eukaryotic cells. Also provided is a rapid and convenient method of detecting eukaryotic cells in which the LTVEC has correctly targeted and modified the desired endogenous gene(s) or chromosomal locus (loci) as well as the use of these cells to generate organisms bearing the genetic modification.Type: GrantFiled: October 4, 2013Date of Patent: November 25, 2014Assignee: Regeneron Pharmaceuticals Inc.Inventors: Andrew J. Murphy, George D. Yancopoulos, Margaret Karow, Lynn Macdonald, Sean Stevens, Aris N. Economides, David M. Valenzuela
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Publication number: 20140344963Abstract: A spermatogonial stem cell line that is derived from testes of rats characterized by a desirable genetic background can serve as a source for cells to transplant into male-sterile recipient animals that are immuno-compatible with the spermatogonial line. Rat cells thus transplanted readily develop into fertilization-competent, haploid male gametes, with little or no endogenous sperm competition generated by the testes of the male-sterile recipient. This approach, constituting the first vector system for the use of rat spermatogonial lines from in vitro culture in generating mutant rats on a desired genetic background, effects maximal germline transmission of donor haplotypes from the transplanted spermatogonial cells.Type: ApplicationFiled: May 23, 2014Publication date: November 20, 2014Applicant: Board of Regents of The University of Texas SystemInventor: Franklin Kent Hamra
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Publication number: 20140335579Abstract: The present invention relates to polynucleotides from Cochliobolus heterostrophus C5, Cyanothece sp. CCY0110, Mycocentrospora acerin and Hyaloperonospora parasitica, which code for desaturases and which can be employed for the recombinant production of polyunsaturated fatty acids. The invention furthermore relates to vectors, host cells and transgenic nonhuman organisms which comprise the polynucleotides according to the invention, and to the polypeptides encoded by the polynucleotides. The invention furthermore relates to antibodies against the polypeptides according to the invention. Finally, the invention also relates to production processes for the polyunsaturated fatty acids and for oil, lipid and fatty acid compositions and to their use as drugs, cosmetics, foodstuffs, feedstuffs, preferably fish food, or food supplements.Type: ApplicationFiled: July 23, 2014Publication date: November 13, 2014Inventors: Toralf Senger, Jörg Bauer, Johnathan A. Napier
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Publication number: 20140338007Abstract: Transgenic artiodactyls are described as well as methods of making and using such artiodactyls.Type: ApplicationFiled: July 14, 2014Publication date: November 13, 2014Applicant: Recombinetics, Inc.Inventors: Scott C. Fahrenkrug, Daniel F. Carlson, Aron M. Geurts
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Patent number: 8884095Abstract: The present invention relates to the field of neurological disorders and more particularly to the field of neuropsychiatric disorders. The invention provides non-human, transgenic animal models for brain disorders such as schizophrenia, bipolar disorders, compulsive disorders, addictive disorders and the like. The animals also have applications in the field of GABA neurotransmission and other disorders in which GABA-dependent gene regulation has a role.Type: GrantFiled: July 17, 2010Date of Patent: November 11, 2014Assignee: Ann & Robert H. Lurie Children's Hospital of ChicagoInventor: Jhumku Kohtz
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Patent number: 8883150Abstract: The present invention provides a high affinity, antigen-specific, soluble heavy chain-only antibody which: lacks hallmark camelid-related amino acid substitutions and has FR2 substitutions which are not found in antibodies which comprise heavy and light chain; shows increased net hydrophobicity within CDR1 and an increased number of charged amino acids present in CDR3; and comprises one or more amino acid substitutions within the framework ?-pleated sheet leading to increased net hydrophobicity within FR1 and increased number of charged amino acids present in FR3. Also provided are VH domains having the same properties, gene segments for their production, methods for their production, transgenic animals and uses of the antibody of the VH domains in therapy.Type: GrantFiled: March 19, 2010Date of Patent: November 11, 2014Assignee: Erasmus University Medical CenterInventors: Roger Kingdon Craig, Franklin Gerardus Grosveld, Richard Wilhelm Janssens, Dubravka Drabek, Tao Chen, Ernie De Boer
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Publication number: 20140331345Abstract: The present invention provides a 5 kb sequence of porcine ROSA26 locus, which can be used for site-specific integration of an exogenous gene into a pig genome. The present invention also provides a gene targeting vector with a 3? and 5? arm of the porcine ROSA26 sequence, wherein a target gene can be inserted between the 3? and 5? arm sequence. The gene targeting vector can be used to generate transgenic pigs with stable and ubiquitous expression of the target gene.Type: ApplicationFiled: May 4, 2013Publication date: November 6, 2014Inventors: Qingran Kong, Meiling Wu, Zhonghua Liu
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Publication number: 20140331342Abstract: The present invention develops a novel method for controlling mosquito populations. Culicinae mosquitoes carrying one or more loci of transformant Tra-2 RNAi constructs which target to mosquito Transformer-2 locus in respective or none respective Culicinae mosquitoes. Tra-2 sequences used to assemble Tra-2 RNAi recombinant constructs are Tra-2 gene sequences of Culicinae mosquitoes and can be derived from endogenous or exogenous sequences. The Tra-2 RNAi expression is conditional, wherein the expression causing a knockdown effect into the endogenous Tra-2 gene results in mortality of X (m) chromosome bearing sperms and produces maleness mosquito population in the nature environmental of the species.Type: ApplicationFiled: December 29, 2011Publication date: November 6, 2014Inventors: Duong Thanh Hoang, Kim Phuc Hoang
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Publication number: 20140325690Abstract: The invention provides Assay Vertebrates comprising a human antigen or epitope knock-in for testing antibodies comprising human variable regions and generated in a related Antibody-Generating Vertebrate. The invention also provides kits and methods involving these vertebrates and antibodies. The invention provides for superior assay models and assay methods of chimaeric and other test antibodies comprising human variable regions.Type: ApplicationFiled: April 28, 2014Publication date: October 30, 2014Applicant: Kymab LimitedInventors: Allan Bradley, E-Chiang Lee, Qi Liang
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Patent number: 8871996Abstract: Genetically modified non-human animals and methods and compositions for making and using them are provided, wherein the genetic modification comprises a humanization of an extracellular loop of an endogenous NaV channel gene, in particular a humanization of the one or more extracellular pore loops of a NaV1.7 channel protein. Genetically modified non-human animals are also provided, wherein the genetic modification comprises replacement of an endogenous NaV channel gene, in particular a replacement of the endogenous NaV1.7 gene with a human NaV1.7 gene, and wherein the genetically modified non-human animals are capable of generating action potentials and communicating through the excitable cells of the genetically modified non-human animals via the expressed human or humanized NaV1.7 protein the surface of the excitable cells. Genetically modified mice are described, including mice that express the human or humanized NaV1.7 gene from the endogenous NaV1.Type: GrantFiled: June 8, 2011Date of Patent: October 28, 2014Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Lynn Macdonald, Andrew J. Murphy, Michael L. LaCroix-Fralish, Nicole M. Alessandri Haber
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Publication number: 20140317767Abstract: The present invention provides a perennial lineage engendered with hyperdominant traits that express consistent penetrance in all descendants of a founder organism. A genetic construct containing one or more genetic elements encoding a self-regulating feedback loop generates a regulatory RNA, polypeptide, or other gene product at or below a trigger level of concentration in a zygote and indicates with respect to the concentration level whether one or two copies of a genetic construct conferring a hyperdominant trait exist in said zygote.Type: ApplicationFiled: March 12, 2014Publication date: October 23, 2014Inventor: William Douglas Meadow, JR.
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Publication number: 20140317765Abstract: The invention relates to transgenic birds capable of producing chimeric immunoglobulins, with a combination of human and avian sequence, in their B cells. In some embodiments, the birds are chickens. When challenged with an antigen, the transgenic avians produce antigen-specific functional antibodies. The invention also relates to light chain immunoglobulin transgenes for making such transgenic avians, as well as methods and vectors for disrupting endogenous immunoglobulin loci in birds.Type: ApplicationFiled: August 30, 2012Publication date: October 23, 2014Applicant: SYNAGEVA BIOPHARMA CORP.Inventors: Philip A. Leighton, Emily J. Cadera
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Publication number: 20140310828Abstract: Compositions and methods are provided for modifying a rat genomic locus of interest using a large targeting vector (LTVEC) comprising various endogenous or exogenous nucleic acid sequences as described herein. Compositions and methods for generating a genetically modified rat comprising one or more targeted genetic modifications in their germline are also provided. Compositions and methods are provided which comprise a genetically modified rat or rat cell comprising a targeted genetic modification in the rat interleukin-2 receptor gamma locus, the rat ApoE locus, the rat Rag2 locus, the rat Rag1 locus and/or the rat Rag2/Rag1 locus. The various methods and compositions provided herein allows for these modified loci to be transmitted through the germline.Type: ApplicationFiled: April 16, 2014Publication date: October 16, 2014Inventors: Jeffrey D. Lee, Alexander O. Mujica, Wojtek Auerbach, Ka-Man Venus Lai, David M. Valenzuela, George D. Yancopoulos
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Publication number: 20140304847Abstract: The present invention relates to a method for modifying a target sequence in the genome of a mammalian cell, the method comprising the step of introducing into a mammalian cell: a. one or more compounds that introduce double-strand breaks in said target sequence; b. one or more DNA molecules comprising a donor DNA sequence to be incorporated by homologous recombination into the genomic DNA of said mammalian cell within said target sequence, wherein said donor DNA sequence is flanked upstream by a first flanking element and downstream by a second flanking element, wherein said first and second flanking element are different and wherein each of said first and second flanking sequence are homologous to a continuous DNA sequence on either side of the double-strand break introduced by said one or more compounds of a. within said target sequence in the genome of said mammalian cell; and c.Type: ApplicationFiled: June 6, 2012Publication date: October 9, 2014Inventors: Ralf Kühn, Wolfgang Wurst
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Publication number: 20140304843Abstract: Provided is a method of assessing a potential for development of Dravet syndrome with high accuracy, and use thereof. The method according to the present invention of assessing a potential for development of Dravet syndrome includes, with use of a sample taken from a subject, detecting whether or not a mutation is on ?-subunit type 1 of voltage-gated sodium ion channel NaV1.1, and detecting whether or not a mutation is on ?-subunit type 1 of voltage-gated calcium ion channel CaV2.1.Type: ApplicationFiled: June 23, 2014Publication date: October 9, 2014Inventors: Iori Ohmori, Mamoru Ouchida
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Publication number: 20140298504Abstract: The present invention is transgenic chickens obtained from long-term cultures of avian PGCs and techniques to produce and transgenic birds derived from prolonged PGC cultures. In some embodiments, these PGCs can be transfected with genetic constructs to modify the DNA of the PGC, specifically to introduce a transgene encoding an exogenous protein. When combined with a host avian embryo by known procedures, those modified PGCs are transmitted through the germline to yield transgenic offspring. This invention includes compositions comprising long-term cultures of PGCs and offspring derived from them that are genetically modified.Type: ApplicationFiled: March 7, 2014Publication date: October 2, 2014Inventors: Marie-Cecile Van de Lavoir, Philip A. Leighton
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Publication number: 20140298493Abstract: The invention concerns the development of a PIK3CA H1047R knock-in non-human animal breast cancer model, and its use for identification of a spontaneous loss-of-function TP53 mutation involved in spindle cell tumor formation. The invention further concerns the identification of additional somatic mutations and copy number aberrations in the breast tumors using this model, and methods and means for the diagnosis and treatment of breast cancer.Type: ApplicationFiled: July 26, 2012Publication date: October 2, 2014Inventor: Somasekar Seshagiri
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Publication number: 20140298505Abstract: The present invention relates to a nucleic acid molecule encoding (I) a polypeptide having the activity of an endonuclease, which is (a) a nucleic acid molecule encoding a polypeptide comprising or consisting of the amino acid sequence of SEQ ID NO: 1; (b) a nucleic acid molecule comprising or consisting of the nucleotide sequence of SEQ ID NO: 2; (c) a nucleic acid molecule encoding an endonuclease, the amino acid sequence of which is at least 70% identical to the amino acid sequence of SEQ ID NO: 1; (d) a nucleic acid molecule comprising or consisting of a nucleotide sequence which is at least 50% identical to the nucleotide sequence of SEQ ID NO: 2; (e) a nucleic acid molecule which is degenerate with respect to the nucleic acid molecule of (d); or (f) a nucleic acid molecule corresponding to the nucleic acid molecule of any one of (a) to (e) wherein T is replaced by U; (II) a fragment of the polypeptide of (I) having the activity of an endonuclease.Type: ApplicationFiled: June 6, 2012Publication date: October 2, 2014Inventor: Ralf Kühn
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Publication number: 20140298501Abstract: A modified arthropod, an arthropod-modifying bacterium, and use thereof as an agent for control of diseases transmitted by arthropods, particularly mosquitoes, is provided. More specifically, an isolated arthropod-adapted Wolbachia bacterium capable of modifying one or more biological properties of a mosquito host is provided. The modified arthropod may be characterized as having a shortened life-span, a reduced ability to transmit disease, a reduced susceptibility to a pathogen, a reduced fecundity, and/or a reduced ability to feed from a host, when compared to a corresponding wild-type arthropod.Type: ApplicationFiled: June 14, 2014Publication date: October 2, 2014Inventors: Scott Leslie O'Neill, Conor James McMeniman, Karyn Nicole Johnson, Elizabeth Ann McGraw, Luciano A. Moreira, Peter Anthony Ryan, Brian Herbert Kay, Jeremy Colin Brownlie
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Publication number: 20140289881Abstract: The present disclosure provides methods and compositions relating to a polynucleotide comprising a dsRNA region that is complementary to a particular region of the NS1 gene segment in the influenza virus genome that targets a sequence comprising two overlapping reading frames, one encoding NS1 and the second encoding the NEP polypeptide. Thus, the polynucleotide of the invention is able to target two message RNAs and is effective at inhibiting the replication of influenza virus in a cell.Type: ApplicationFiled: March 13, 2014Publication date: September 25, 2014Inventors: Timothy James Doran, Scott Geoffrey Tyack
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Publication number: 20140289878Abstract: A method for producing a model animal which has a desired lifetime, and in which a predetermined biological reaction can be induced, and a model animal are provided. The present invention produces a first individual in which a gene of interest is heterozygously deficient using a first ES cell from a non-human mammalian animal. Meanwhile, a fragment containing a homologous gene that has homology to the gene of interest is made, a second ES cell constituted so that a predetermined region on X chromosome of the animal can be substituted is used, and the fragment is introduced into the second ES cell to generate a substituted ES cell in which the predetermined region has been substituted with the fragment. A second individual is produced using the substituted ES cell. The first individual and the second individual are mated with each other to produce a model animal.Type: ApplicationFiled: June 19, 2012Publication date: September 25, 2014Applicant: NATIONAL UNIVERSITY CORPORATION KUMAMOTO UNIVERSITYInventors: Masaki Ohmuraya, Kimi Araki
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Publication number: 20140289882Abstract: The present inventions are directed to compositions and methods regarding the reprogramming of other cells (such as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), MSCs, fibroblasts, hematopoietic stem cells, endothelian stem cells, adipocytes, chondrocytes, osteoblasts, osteoclasts and endothelial cells) into chondrogenic cells without introducing exogenous genes to the samples. In particular, the present inventions are directed to transducible materials that are capable of transducing into the biological samples but are not genes or causing genetic modifications. The present inventions also are directed to methods of reprogramming the path of biological samples or treating diseases using the tranducible compositions thereof.Type: ApplicationFiled: July 19, 2012Publication date: September 25, 2014Applicants: OREGON HEALTH AND SCIENCE UNIVERSITY, VIVOSCRIPT, INC.Inventors: Yong Zhu, Shili Wu, Jun Bao, Cong-Qiu Chu
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Publication number: 20140289880Abstract: The present invention is transgenic chickens obtained from long-term cultures of avian PGCs and techniques to produce and transgenic birds derived from prolonged PGC cultures. In some embodiments, these PGCs can be transfected with genetic constructs to modify the DNA of the PGC, specifically to introduce a transgene encoding an exogenous protein. When combined with a host avian embryo by known procedures, those modified PGCs are transmitted through the germline to yield transgenic offspring. This invention includes compositions comprising long-term cultures of PGCs that can be genetically modified by gene targeting, that can accept large amounts of foreign DNA and that contribute to the germline of recipient embryos.Type: ApplicationFiled: March 7, 2014Publication date: September 25, 2014Inventors: Marie-Cecile Van de Lavoir, Philip A. Leighton
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Patent number: 8841508Abstract: The present invention provides a non-human mammalian animal model for type 2 diabetes, which spontaneously develops a pathological condition similar to human type 2 diabetes of a non-obese type seen in some Japanese people. The non-human mammalian animal model for type 2 diabetes according to the present invention is deficient in a Cdkal1 gene function on the chromosome of the ? cell of the pancreas.Type: GrantFiled: November 10, 2010Date of Patent: September 23, 2014Assignees: National University Corporation, Kumamoto UniversityInventors: Kazuhito Tomizawa, Fanyan Wei
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Publication number: 20140283150Abstract: The invention discloses methods for the generation of chimaeric human-non-human antibodies and chimaeric antibody chains, antibodies and antibody chains so produced, and derivatives thereof including fully humanised antibodies; compositions comprising said antibodies, antibody chains and derivatives, as well as cells, non-human mammals and vectors, suitable for use in said methods.Type: ApplicationFiled: March 18, 2013Publication date: September 18, 2014Applicant: Kymab LimitedInventors: Allan Bradley, E-Chiang Lee, Qi Liang, Wei Wang, Dominik Spensberger, Hui Liu, Jasper Clube
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Publication number: 20140283154Abstract: The present invention relates to methods of facilitating the expression of recombinant polypeptides from cells, extracellular fluids, extracellular fibers, or any combination thereof, obtained from transgenic insect cells and larvae comprising a bacterial GlcNAc-6-P 2?-epimerase (GNPE), which is capable of converting N-acetyl-D-glucosamine-6-phosphate (GlcNAc-6-P) to N-acetyl-D-mannosamine-6-phosphate (ManNAc-6-P). The invention relates to methods to promote efficient glycoconjugate sialylation, by providing simpler ways to produce large intracellular pools of sialic acid precursors. The invention is also directed to nucleic acids, vectors, and cells comprising nucleic acids encoding polypeptides involved in the synthesis of sialic acid precursors, and cells in combination with nucleic acids encoding glycosyltransferases, including sialyltransferases, to facilitate the production of humanized recombinant glycoproteins.Type: ApplicationFiled: March 14, 2013Publication date: September 18, 2014Inventors: Christoph GEISLER, Donald Jarvis
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Publication number: 20140283155Abstract: Disclosed herein are components, systems and methods for regulating population of multicellular organisms, for example insects.Type: ApplicationFiled: March 12, 2014Publication date: September 18, 2014Inventors: Omar S. Akbari, Katie L. Kennedy, Bruce A. Hay
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Patent number: 8835712Abstract: The present invention provides novel transgenic nonhuman mammals capable of producing human sequence antibodies, as well as methods of producing and using these antibodies.Type: GrantFiled: September 9, 2010Date of Patent: September 16, 2014Assignees: Medarex, L.L.C., Kyowa Hakko Kirin Co., Ltd.Inventors: Kazuma Tomizuka, Isao Ishida, Nils Lonberg, Edward L. Halk
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Patent number: 8829264Abstract: The present invention provides methods for attenuating gene expression in a cell, especially in a mammalian cell, using gene-targeted double stranded RNA (dsRNA), such as a hairpin RNA. The dsRNA contains a nucleotide sequence that hybridizes under physiologic conditions of the cell to the nucleotide sequence of at least a portion of the gene to be inhibited (the “target” gene).Type: GrantFiled: June 18, 2012Date of Patent: September 9, 2014Assignee: Cold Spring Harbor LaboratoryInventors: Gregory J. Hannon, Patrick Paddison, Emily Bernstein, Amy Caudy, Douglas Conklin, Scott Hammond
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Publication number: 20140245466Abstract: The invention provides genetically modified non-human animals that express chimeric human/non-human T cell co-receptor polypeptides (e.g., CD4, CD8?, CD8?), as well as embryos, cells, and tissues comprising the same. Also provided are constructs for making said genetically modified animals and methods of making the same.Type: ApplicationFiled: February 20, 2014Publication date: August 28, 2014Applicant: REGENERON PHARMACEUTICALS, INC.Inventors: Lynn MACDONALD, Andrew J. MURPHY, Naxin TU, Vera VORONINA, Cagan GURER
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Publication number: 20140245467Abstract: The invention provides genetically modified non-human animals that express chimeric human/non-human MHC I and MHC II polypeptides and/or human or humanized ?2 microglobulin polypeptide, as well as embryos, cells, and tissues comprising the same. Also provided are constructs for making said genetically modified animals and methods of making the same. Methods of using the genetically modified animals to study various aspects of human immune system are provided.Type: ApplicationFiled: February 20, 2014Publication date: August 28, 2014Applicant: Regeneron Pharmaceuticals, Inc.Inventors: Lynn MACDONALD, Andrew J. MURPHY, Vera VORONINA, Cagan GURER