Method Of Making A Transgenic Nonhuman Animal Patents (Class 800/21)
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Patent number: 8124830Abstract: The present invention provides a substantially purified growth differentiation factor (GDF) receptor, including a GDF-8 (myostatin) receptor, as well as functional peptide portions thereof. In addition, the invention provides a virtual representation of a GDF receptor or a functional peptide portion thereof. The present invention also provides a method of modulating an effect of myostatin on a cell by contacting the cell with an agent that affects myostatin signal transduction in the cell. In addition, the invention provides a method of ameliorating the severity of a pathologic condition, which is characterized, at least in part, by an abnormal amount, development or metabolic activity of muscle or adipose tissue in a subject, by modulating myostatin signal transduction in a muscle cell or an adipose tissue cell in the subject.Type: GrantFiled: January 28, 2009Date of Patent: February 28, 2012Assignee: The Johns Hopkins University School of MedicineInventors: Se-Jin Lee, Alexandra C. McPherron
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Publication number: 20120047588Abstract: Methods are disclosed in which the expression of a specific gene, or combinations of genes, is controlled spatially and temporally to develop intra- and interspecies chimeras. A transgenic EC/ES/P/iPS cell line is created which conditionally expresses a suicide or compromiser gene configured to compromise all cell lineages except that corresponding to a target tissue/organ. The EC/ES/P/iPS cell line is injected into donor embryos having a specific target gene deficiency or embryos genetically engineered to be complementary compromised in lineages corresponding to the target tissue/organ cell lineages of the EC/ES/P/iPS line. One or more stimuli is provided to the embryo to activate compromiser genes for ablation of non-target tissues/organs of the EC/ES/P/iPS line and target tissues/organs of the host embryo, resulting in a chimeric animal having target tissues/organs derived from the genotype of the transgenic cell line and all remaining tissues/organs derived from the donor embryo.Type: ApplicationFiled: September 1, 2011Publication date: February 23, 2012Applicant: THE CURATORS OF THE UNIVERSITY OF MISSOURIInventors: Chongbei Zhao, Andras Nagy, John K. Critser
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Publication number: 20120047589Abstract: Methods to introduce genetic material, such as DNA, to embryos, are disclosed. In some embodiments, the method involves preparing the pregnant mother to receive the genetic material into a blood transport vessel which passes to the embryo, avoiding a maternal capillary bed and introducing the material under low pressure so as not to kill the pregnant animal. The effectiveness of the method is such that the nucleic acid has been expressed in all the cells of the embryo and in the postnatal mouse, including the primordial germ cells, thus making the nucleic acid germ line heritable.Type: ApplicationFiled: October 27, 2011Publication date: February 23, 2012Inventors: Theresa E. Gratsch, J. Matthew Velkey, Lisa S. D. Emmett, K. Sue O'Shea
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Publication number: 20120042401Abstract: Disclosed is a method for introducing a mutation into a gene, which comprises the following steps: a homologous recombination step of carrying out the homologous recombination between a target gene into which the mutation is to be introduced and a target recombinant vector, thereby substituting an exon in the target gene into which the mutation is to be introduced by a target DNA sequence in the target recombinant vector; and a mutation introduction step of carrying out the specific recombination between the target DNA sequence in the resulting target recombinant gene and a mutation introduction cassette of a mutation introduction vector carrying a mutated DNA sequence containing a mutant exon by the intervening action of Cre recombinase to substitute the target DNA sequence by the mutated DNA in the mutation introduction cassette, thereby producing a mutation-introduced gene into which the mutant DNA sequence has been introduced.Type: ApplicationFiled: October 23, 2009Publication date: February 16, 2012Inventors: Shinichi Hirose, Masanobu Deshimaru, Kimi Araki
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Publication number: 20120036591Abstract: Methods are provided for producing a primate oocyte in vitro. The methods include removing nuclear DNA from a recipient primate oocyte from a first primate in a manner that does not lower levels of maturation promoting factor (MPF) to form an enucleated recipient primate oocyte. The recipient primate oocyte is enucleated using a non-UV-based spindle imaging system. Nuclear genetic material or DNA including chromosomes from a donor primate oocyte arrested at metaphase II from a second primate is isolated in the form of the karyoplast and introduced into the enucleated recipient primate oocyte. Introduction of the chromosomes is performed using a fusogenic agent or electroporation to produce a hybrid oocyte.Type: ApplicationFiled: April 22, 2010Publication date: February 9, 2012Inventor: Shoukhrat M. Mitalipov
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Patent number: 8110719Abstract: Genetically engineered conditional knock-out mice having conditional disruption of the Abi1/Hssh3bp1 gene are disclosed along with methods of making and using same.Type: GrantFiled: April 27, 2009Date of Patent: February 7, 2012Assignee: New York Blood Center, Inc.Inventor: Leszek Kotula
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Publication number: 20120030781Abstract: A polynucleotide consisting of the base sequence of SEQ ID NO:2, or a complementary strand thereto, wherein the X is one of the group being defined by the bases A, C or T. A primer and a probe specific for that polynucleotide, wherein the primer and/or probe contains at least 10 consecutive nucleotides, and finally use of the probe for proving parkinsonism inheritance.Type: ApplicationFiled: June 29, 2011Publication date: February 2, 2012Inventors: Jan O. Aasly, Zbigniew K. Wszolek, Matthew J. Farrer
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Publication number: 20120030782Abstract: 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 germline transgenic animals by direct injection of nucleic acid molecules into animals.Type: ApplicationFiled: October 4, 2011Publication date: February 2, 2012Applicant: The Regents of The University of MichiganInventors: Lisa S. D. Emmett, Theresa Gratsch, K. Sue O'Shea, J. Matthew Velkey, Michael J. Welsh, William Wu
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Publication number: 20120030779Abstract: Disclosed herein is a non-human animal model of protein aggregation cardiomyopathy. Also disclosed are compo-sitions and methods of treating or preventing a condition in a subject caused or exacerbated by reductive stress. Also disclosed are compositions and methods of predicting, detecting, or monitoring reductive stress in a subject.Type: ApplicationFiled: January 18, 2008Publication date: February 2, 2012Applicant: UNIVERSITY OF UTAH RESEARCH FOUNDTIONInventors: Ivor J. Benjamin, Namakkal S. Rajasekaran, Thomas P. Kennedy
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Patent number: 8101816Abstract: The invention provides a new reproducible transgenic mouse model for the study of iron accumulation in the body. In particular, the invention concerns the study of iron overload in an RGMc knockout mouse model and its use in drug discovery and research.Type: GrantFiled: July 22, 2005Date of Patent: January 24, 2012Assignee: Novartis Forschungsstiftung, Zweigniederalassung Friedrich Miescher Institute for Biomedical ResearchInventor: Silvia Arber
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Publication number: 20120017290Abstract: Disclosed herein are methods and compositions for genome editing of a Rosa locus, using fusion proteins comprising a zinc-finger protein and a cleavage domain or cleavage half-domain. Polynucleotides encoding said fusion proteins are also provided, as are cells comprising said polynucleotides and fusion proteins.Type: ApplicationFiled: April 25, 2011Publication date: January 19, 2012Inventors: Xiaoxia Cui, Gregory Davis, Philip D. Gregory, Michael C. Holmes, Edward J. Weinstein
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Publication number: 20120017289Abstract: The present invention provides a novel method of generating knock down models by electroporation of shRNA construct into the testis. The present invention provides an ethically superior, non-surgical, user friendly rapid method for the generation of permanent lines of shRNA knock down non human vertebrates. This invention is ethically superior as it does not involve any loss of animal life and drastically minimizes the production time and use of animals. Current techniques for making knockout models are cumbersome, require trained personnel, costly infrastructure and require hundreds of eggs collected after killing several females. In contrast, this method neither involves any costly infrastructure nor requires trained personnel. The invention also relates to the quick incorporation of shRNA gene construct into the germline of a species so that shRNA is inheritable.Type: ApplicationFiled: October 1, 2010Publication date: January 19, 2012Applicant: National Institute of ImmunologyInventors: Subeer Suhash Majumdar, Deepika Sharma, Neerja Wadhwa
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Publication number: 20110314563Abstract: A non-human mammal containing an endogenous lambda light chain gene locus, an endogenous kappa light chain gene locus and an endogenous heavy chain gene locus, each of which can re-arrange so that immunoglobulin heavy and light chain genes are formed and expressed in B-cells following antigen challenge but said loci have been mutated so that the ability to form functional immunoglobulin tetramers comprising re-arranged heavy and light chains produced from said mutated loci has been substantially reduced or eliminated.Type: ApplicationFiled: November 30, 2009Publication date: December 22, 2011Inventors: Roger Kingdon Craig, Franklin Gerardus Grosveld, Richard Wilhelm Janssens, Mariuns Johannes Van Haperen
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Publication number: 20110307967Abstract: Mice comprising a human p16 transgene operably linked to an inducible promoter and capable of controlled expression of p16 are provided. Also provided are cells, tissues, and organs obtainable from such mice, and methods for producing p16 transgenic mice.Type: ApplicationFiled: June 10, 2011Publication date: December 15, 2011Applicant: Fox Chase Cancer CenterInventor: Greg H. Enders
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Publication number: 20110307966Abstract: 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: ApplicationFiled: June 8, 2011Publication date: December 15, 2011Applicant: Regeneron Pharmaceuticals, Inc.Inventors: Lynn Macdonald, Andrew J. Murphy, Michael L. LaCroix-Fralish, Nicole M. Alessandri Haber
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Publication number: 20110307968Abstract: Methods and compositions are described for making phenotypically female fertile animals from XY donor cells and suitable host embryos. Culture media and methods are provided for maintaining XY donor cells in culture that after introduction into a host embryo and gestation in a suitable host will result in fertile XY female animals. Methods and compositions are described for making fertile female animals in an F0 generation from a donor XY cell and a host embryo, as are methods for making F1 progeny that are homozygous for a modification from a heterozygous F0 fertile male and a heterozygous F0 fertile female sibling.Type: ApplicationFiled: June 10, 2011Publication date: December 15, 2011Applicant: Regeneron Pharmaceuticals, Inc.Inventors: Wojtek AUERBACH, Thomas DeChiara, William Poueymirou, David Frendewey, David Valenzuela
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Patent number: 8076138Abstract: The invention provides methods employing iterative cycles of recombination and selection/screening for evolution of whole cells and organisms toward acquisition of desired properties. Examples of such properties include enhanced recombinogenicity, genome copy number, and capacity for expression and/or secretion of proteins and secondary metabolites.Type: GrantFiled: October 15, 2009Date of Patent: December 13, 2011Assignee: Codexis Mayflower Holdings, LLCInventors: Stephen DelCardayre, Matthew B. Tobin, Willem P. C. Stemmer, Jon E. Ness, Jeremy S. Minshull, Phillip A. Patten, Venkiteswatan Mani Subramanian, Linda A. Castle, Claus M. Krebber, Steven H. Bass, Ying-Xin Zhang, Anthony R. Cox, Gjalt W. Huisman, Ling Yuan, Joseph A. Affholter
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Publication number: 20110302666Abstract: A spermatogonial stem cell line that is derived from testes 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: December 1, 2009Publication date: December 8, 2011Inventor: Franklin Kent Hamra
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Patent number: 8071839Abstract: The present invention relates to transgenic non-human mammals comprising a polynucleotide encoding a human or humanized C5aR. The invention also relates to use of the transgenic non-human mammals in methods of screening for agonists, inverse agonists and antagonists of human C5aR and for testing efficacy of C5aR agonists, inverse agonists and antagonists in various animal models of disease.Type: GrantFiled: December 24, 2004Date of Patent: December 6, 2011Assignee: G2 Inflammation Pty LtdInventor: Charles Reay Mackay
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Publication number: 20110296545Abstract: Particular aspects show that the signal peptide remains intact on the mature CD18 molecule on ruminant leukocytes rendering these cells susceptible to cytolysis by Lkt. Comparative amino acid sequence analysis of the signal peptide of CD18 of eight ruminants and five non-ruminants revealed that the ruminant CD18 signal peptides contain ‘cleavage-inhibiting’ glutamine (Q), compared to ‘cleavage-conducive’ glycine in non-ruminants, at position ?5 relative to the cleavage site. Mutagenesis of Q at position ?5 of the bovine CD18 signal peptide to G resulted in the abrogation of Lkt-mediated cytolysis of transfectants expressing bovine CD18 carrying the Q(?5)G mutation. Provided is novel technology to clone cattle and other ruminants expressing CD18 without the signal peptide on their leukocytes, providing ruminants that are less susceptible to M. haemolytica. Methods for treating conditions and/or diseases associated with M. haemolytica (e.g.Type: ApplicationFiled: February 2, 2010Publication date: December 1, 2011Applicant: Washington State UniversityInventors: Subramaniam Srikumaran, Sudarvili Shanthalingam
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Patent number: 8067664Abstract: The present invention relates to transgenic animals, as well as compositions and methods relating to the characterization of gene function. Specifically, the present invention provides transgenic mice comprising disruptions in PRO224, PRO9783, PRO1108, PRO34000, PRO240, PRO943, hu A33, PRO230, PRO178, PRO1199, PRO4333, PRO1336, PRO19598, PRO1083, hu TRPM2 or PRO1801 genes. Such in vivo studies and characterizations may provide valuable identification and discovery of therapeutics and/or treatments useful in the prevention, amelioration or correction of diseases or dysfunctions associated with gene disruptions such as neurological disorders; cardiovascular, endothelial or angiogenic disorders; eye abnormalities; immunological disorders; oncological disorders; bone metabolic abnormalities or disorders; lipid metabolic disorders; or developmental abnormalities.Type: GrantFiled: December 13, 2004Date of Patent: November 29, 2011Assignee: Genentech, Inc.Inventor: Wenhu Huang
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Patent number: 8067666Abstract: A model rodent animal with a phenotype in which hair growing after birth is black, with the animal spontaneously developing white hair after aging. By way of example, the model rodent animal may have a genotype in which an activated RET gene is genetically inserted in a heterozygous form and the endothelin receptor B gene is deficient in a heterozygous form.Type: GrantFiled: February 10, 2006Date of Patent: November 29, 2011Assignee: Chubu University Educational FoundationInventor: Masashi Kato
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Publication number: 20110289611Abstract: The present invention relates to a Drosophila in vitro system which was used to demonstrate that dsRNA is processed to RNA segments 21-23 nucleotides (nt) in length. Furthermore, when these 21-23 nt fragments are purified and added back to Drosophila extracts, they mediate RNA interference in the absence of long dsRNA. Thus, these 21-23 nt fragments are the sequence-specific mediators of RNA degradation. A molecular signal, which may be their specific length, must be present in these 21-23 nt fragments to recruit cellular factors involved in RNAi. This present invention encompasses these 21-23 nt fragments and their use for specifically inactivating gene function. The use of these fragments (or chemically synthesized oligonucleotides of the same or similar nature) enables the targeting of specific mRNAs for degradation in mammalian cells, where the use of long dsRNAs to elicit RNAi is usually not practical, presumably because of the deleterious effects of the interferon response.Type: ApplicationFiled: October 4, 2010Publication date: November 24, 2011Inventors: Thomas Tuschl, Phillip D. Zamore, Phillip A. Sharp, David P. Bartel
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Publication number: 20110277049Abstract: Genetic material is derived from animals post-mortem, and used in nuclear transfer processes to produce cloned embryos and live cloned animals having genetic make-ups identical to the post mortem animals. The method has particular applicability to the management and breeding of livestock, to the production of animals having desired genetic traits, and to the integration of those genetic traits into selective breeding operations.Type: ApplicationFiled: July 21, 2011Publication date: November 10, 2011Applicant: The University of Georgia Research Foundation, IncInventors: Steven L. Stice, John Gibbons, Donald Respess
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Publication number: 20110277043Abstract: The present invention relates to polynucleotides from Cochliobolus heterostrophus C5, Cyanothece sp. CCY0110, Mycocentrospora acerina 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: December 8, 2009Publication date: November 10, 2011Applicant: BASF Plant Science Company GmbHInventors: Toralf Senger, Jörg Bauer, Johnathan A. Napier
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Publication number: 20110268747Abstract: A non-human transgenic animal having a polynucleotide encoding an STXBP1 polypeptide, which polynucleotide is operably linked to a promoter, wherein said transgenic animal has greater than wild-type expression of the STXBP1 polypeptide in at least one brain region, as well as related vectors, methods of producing transgenic animals, in vitro and in vivo screening methods for potential therapeutic agents, and methods for treating and diagnosing neuropsychiatric illness are disclosed.Type: ApplicationFiled: August 18, 2009Publication date: November 3, 2011Inventors: Maria Jose Guerrero Martinez, Laureano Simon Buela, Marcel Ferrer-Alcon, Antonio Martinez Martinez, Jose Javier Meana, Luis Felipe Callado, Leyre Uriguen
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Publication number: 20110265194Abstract: The invention provides a new reproducible genetically-modified mouse model for the study of non-alcoholic fatty liver disease. In particular, the invention concerns the study of non-alcoholic fatty liver disease in an THEM5 knockout mouse model and its use in drug discovery and research.Type: ApplicationFiled: October 29, 2009Publication date: October 27, 2011Inventors: Bettina Duemmler, Brian Arthur Hemmings, Elena Zhuravleva
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Publication number: 20110265192Abstract: A sensor system for detecting the activation of specific nuclear receptors in a tissue of an animal is provided. The nuclear receptor sensor system comprises a sensor component comprising a nuclear receptor or part thereof coupled to a DNA-binding domain, and a reporter component comprising a reporter gene. Transgenic animals, such as a transgenic pig is provided, which comprises the components of the nuclear receptor sensor system in its genome. Also methods of producing the transgenic animal is provided as well as use of the transgenic animal for evaluating the activity of a nuclear receptor in vivo.Type: ApplicationFiled: September 3, 2009Publication date: October 27, 2011Applicants: SYDDANSK UNIVERSITET, AARHUS UNIVERSITETInventors: Lars Axel Bolund, Karsten Kristiansen, Jacob Giehm Mikkelsen, Nicklas Heine Staunstrup
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Publication number: 20110265198Abstract: Disclosed herein are methods and compositions for genome editing of a Rosa locus, using fusion proteins comprising a DNA binding domain and a cleavage domain or cleavage half-domain. Polynucleotides encoding said fusion proteins are also provided, as are cells comprising said polynucleotides and fusion proteins.Type: ApplicationFiled: April 25, 2011Publication date: October 27, 2011Inventors: Philip D. Gregory, Michael C. Holmes
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Publication number: 20110258715Abstract: It is revealed that an organ such as pancreas can be regenerated by utilizing a fact that the deficiency of an organ is complemented by injecting an induced pluripotent stem cell (iPS cell) into a developed blastocyst in a blastocyst complementation method. Thus, the present invention has solved the above-described object. This provides a method for producing a target organ, using an iPS cell, in a living body of a non-human mammal having an abnormality associated with a lack of development of the target organ in a development stage, the target organ produced being derived from a different individual mammal that is an individual different from the non-human mammal.Type: ApplicationFiled: August 21, 2009Publication date: October 20, 2011Applicant: THE UNIVERSITY OF TOKYOInventors: Hiromitsu Nakauchi, Toshihiro Kobayashi, Tomoyuki Yamaguchi, Sanae Hamanaka
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Publication number: 20110258710Abstract: 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: ApplicationFiled: June 7, 2011Publication date: October 20, 2011Applicant: REGENERON PHARMACEUTICALS, INC.Inventors: ANDREW J. MURPHY, GEORGE D. YANCOPOULOS
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Patent number: 8034330Abstract: It has been discovered that there are at least two significant antigens present on the cells of animal species such as pigs that elicit an immune or inflammatory response immediately upon implantation into humans or contact with human serum. The first is an ?-galactosyl (Gal) epitope, for example, Gal?(1?3)Gal?(1?4)GlcNac (linear B type 2) or Gal? (1?3)Gal?(1?4)Glc (linear B type 6). The second is an N-glycolylneuraminic acid (NeuGc) structure. By eliminating these epitopes, preferably by genetically engineering the animal so that the epitope is either not produced or is greatly reduced, or by chemical or enzymatic treatment of the animal's cells to remove the epitopes, it is possible to produce organs, tissues and cells suitable for xenotransplantation into humans. Cells can be rendered even more compatible by genetically engineering the animal to express a human complement regulatory protein (inhibitor), such as CD59, on its cells, or to express an excess of a pig complement regulatory protein.Type: GrantFiled: November 20, 2006Date of Patent: October 11, 2011Assignee: RBC Biotechnology, Inc.Inventor: Alex Zhu
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Publication number: 20110247089Abstract: Disclosed herein are homozygously modified organisms and methods of making and using these organisms.Type: ApplicationFiled: April 20, 2011Publication date: October 6, 2011Inventor: Yannick Doyon
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Publication number: 20110239318Abstract: The invention provides methods for producing biofuel from algae, that use fish which have a high capacity of producing and/or accumulating lipids to harvest algae from an algal culture. The invention also provides methods for growing fish that result in a high lipid content. The invention also provides methods for creating fish that have a high capacity of producing and accumulating lipids by breeding and/or recombinant DNA techniques. Also included are transgenic fish that have a higher lipid content than wild-type fish.Type: ApplicationFiled: November 17, 2009Publication date: September 29, 2011Applicant: LiveFuels, Inc.Inventors: David Stephen, Gaye Elizabeth Morgenthaler
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Publication number: 20110239313Abstract: Silkworms which have (i) a DNA encoding a transcriptional regulator operably linked downstream of a promoter of a DNA encoding a protein specifically expressed in the silk gland and (ii) a DNA encoding TRACP5 operably linked downstream of a target promoter of the transcriptional regulator were produced. The result showed that active TRACP5b was produced from the silkworms. This means that TRACP5 produced from the silk gland of the silkworms undergoes processing in the silk gland that is similar to the processing taking place at bone resorption sites.Type: ApplicationFiled: December 28, 2007Publication date: September 29, 2011Applicants: NITTO BOSEKI CO., LTD., NATIONAL INSTITUTE OF AGROBIOLOGICAL SCIENCESInventors: Iwao Kiyokawa, Tatsuya Ohashi, Toshihide Miura, Katsuhiro Katayama, Toshiki Tamura, Isao Kobayashi, Hideki Sezutsu
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Publication number: 20110239319Abstract: The present invention concerns the endonucleases capable of cleaving a target sequence located in a “safe harbor loci”, i.e. a loci allowing safe expression of a transgene. The present invention further concerns the use of such endonucleases for inserting transgenes into a cell, tissue or individual.Type: ApplicationFiled: February 28, 2011Publication date: September 29, 2011Inventors: Olivier DANOS, Aymeric Duclert
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Publication number: 20110236378Abstract: The invention provides knock-in non-human cells and mammals having a genome encoding chimeric antibodies and methods of producing knock-in cells and mammals. Certain aspects of the invention include chimeric antibodies, humanized antibodies, pharmaceutical compositions and kits. Certain aspects of the invention also relate to diagnostic and treatment methods using the antibodies of the invention.Type: ApplicationFiled: September 30, 2009Publication date: September 29, 2011Inventors: Larry Green, Hiroaki Shizuya
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Publication number: 20110239310Abstract: The present invention relates to a transgenic fish having at least one genomically integrated expression cassette containing a 5?-regulatory nucleotide sequence responsive to hormones, particularly estrogenic hormones, connected in a functional manner upstream of a nucleotide sequence encoding a reporter protein. The present invention further relates to methods of using the transgenic fish for various purposes, including, for example: (1) identifying estrogenic endocrine disruptors; (2) monitoring estrogen-like activity of test samples; (3) identifying anti-estrogenic endocrine disruptors; and (4) investigating the effects of endocrine disruptors on liver regeneration. Expression cassettes, host cells, and transgenic cells of aquatic animals are also disclosed.Type: ApplicationFiled: March 24, 2010Publication date: September 29, 2011Applicant: CITY UNIVERSITY OF HONG KONGInventors: Shuk Han CHENG, Xue Ping CHEN
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Publication number: 20110231944Abstract: Provided are a B cell-derived iPS cell generated using a convenient technique, a technology for providing a human antibody at low cost using the iPS cell, an immunologically humanized mouse prepared using cells differentiated from the iPS cell, and the like. Also provided are a cloned cell obtained by contacting a B cell with nuclear reprogramming factors excluding C/EBP? and Pax5 expression inhibiting substances, particularly nucleic acids that encode Oct3/4, Sox2, Klf4 and c-Myc, wherein the cloned cell has an immunoglobulin gene rearranged therein and possesses pluripotency and replication competence (B-iPS cell).Type: ApplicationFiled: September 4, 2009Publication date: September 22, 2011Applicant: RIKENInventors: Hiroshi Watarai, Tomokatsu Ikawa, Fumihiko Ishikawa, Hiroshi Kawamoto, Haruhiko Koseki, Masaru Taniguchi
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Publication number: 20110225662Abstract: The present invention provides an insect expression system that may be used to provide biological control of pest insects and control transmission of infectious diseases transmitted to the human population by insects.Type: ApplicationFiled: March 12, 2010Publication date: September 15, 2011Applicant: BOARD OF TRUSTEES OF THE UNIVERSITY OF ARKANSASInventor: Helen Benes
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Publication number: 20110219465Abstract: The invention provides a novel approach to increase immunoglobulin expression in non-human transgenic animals. For instance, the invention provides a method to increase humanized immunoglobulin production in animals genetically engineered to express one or several human or humanized immunoglobulin transloci. This can be done by overexpressing the apoptosis inhibitor, i.e. a rabbit bcl-2, whose expression is driven by a B-cell specific promoter specifically in the B-cell of the animal, thereby enhancing the survival of B-cells. This invention further relates to a method for selectively enhancing the survival of exogenous B-cells, that is B-cells expressing any immunoglobulin transgene locus, over the survival of endogenous B-cells that do not express the transgene locus. Selectivity is achieved by expressing the apoptosis-inhibitor only within exogenous B-cells, that is, by coupling exogenous immunoglobulin expression with apoptosis inhibitor expression.Type: ApplicationFiled: March 17, 2011Publication date: September 8, 2011Inventors: Roland Buelow, Josef Platzer
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Patent number: 8013208Abstract: This invention provides methods for producing antibodies, wherein the methods comprise the step of administering an immunogen comprising both a target antigen and a background antigen to transgenic animals, into which a gene coding for the background antigen has been introduced. Since immunotolerance to the background antigens have thus been induced in the transgenic animals, the animals efficiently produce antibodies to target antigens.Type: GrantFiled: May 7, 2010Date of Patent: September 6, 2011Assignee: Chugai Seiyaku Kabushiki KaishaInventors: Tatsuhiko Kodama, Kou-ichi Jishage, Nobuo Kamada, Yoshiki Yamada
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Publication number: 20110209231Abstract: The present invention relates to nucleic acid molecules comprising a double-stranded region, and nucleic acid constructs encoding therfor, that are useful for the treatment and/or prevention of influenza. In particular, the present invention relates to nucleic acid constructs encoding a double stranded RNA molecule(s) that can be used to produce transgenic poultry, for example chickens, such that they are at least less susceptible to an avian influenza infection. Also provided are nucleic acid molecules comprising a double-stranded region that can be used as a therapeutic to treat and/or prevent, for example, avian influenza in poultry.Type: ApplicationFiled: May 16, 2008Publication date: August 25, 2011Inventors: Timothy James Doran, James Climie McKay, Robert John Moore, John William Lowenthal, Scott Geoffrey Tyack
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Publication number: 20110209227Abstract: This invention pertains to chemometric methods for the analysis of chemical, biochemical, and biological data, for example, spectral data, for example, nuclear magnetic resonance (NMR) spectra, and their applications, including, e.g., classification, diagnosis, prognosis, etc., especially in the context of bone disorders, e.g., conditions associated with low bone mineral density, e.g., osteoporosis.Type: ApplicationFiled: February 4, 2011Publication date: August 25, 2011Inventors: Jeremy Kirk Nicholson, Elaine Holmes, John Christopher Lindon, Joanne Tracey Brindle, David John Grainger
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Patent number: 8003847Abstract: The genome of the non-human mutant mammal, deficient in an endogenous Sigma receptor, contains a mutation that comprises a disruption in an endogenous Sigma receptor gene, wherein said gene disruption gives rise to a mutant lacking detectable levels of endogenous Sigma receptor. The mutant may be used as a control animal for in vivo tests, as well as a source of cells that can be used in in vitro tests. Mutants deficient in the Sigma-1 receptor can be used as models for in vivo study of disorders of the central nervous system, memory alterations, stress conditions and drug addictions, analgesia processes and neuroprotection. Mutants deficient in the Sigma-2 receptor can be used to study diagnostic or therapeutic tools to fight cancer and/or degenerative processes and/or to design compounds capable of preventing, reducing or alleviating the secondary pathology associated with administration of neuroleptic agents.Type: GrantFiled: December 9, 2003Date of Patent: August 23, 2011Assignee: Laboratorios Del Dr. Esteve, S.A.Inventors: Daniel Zamanillo Castanedo, Lluis Montoliu Jose, Francina Langa Vives, Alfonso Javier Lavado Judez, Victoria Eugenia Tovar Herrador
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Publication number: 20110203007Abstract: The invention relates to novel assays for the in vivo analysis of neurodegenerative diseases and the use of such assays to discover therapies capable of modulating such diseases.Type: ApplicationFiled: February 16, 2010Publication date: August 18, 2011Inventors: Ronald Klein, Phillip Henning, David Wang, Robert Dayton, Jason Tatom, Elysse Orchard
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Patent number: 7994388Abstract: Methods for modulating primordial germ cell (PGC) numbers and/or development in avians are provided. In one embodiment, the presently disclosed subject matter provides a method for modulating primordial germ cells numbers in an avian embryo comprising immunizing a female bird with an antigen associated with primordial germ cells, whereby an egg produced by the female bird comprises a sufficiently high concentration of antibodies specific for the antigen to modulate numbers of endogenous PGCs in an avian embryo present within in the egg. Also provided are methods for producing chimeric avians, methods for increasing the proportion of male birds in a plurality of eggs, methods of producing avian gametes, and methods for enhancing germ line transmission of nucleic acids in birds.Type: GrantFiled: January 16, 2004Date of Patent: August 9, 2011Assignee: North Carolina State UniversityInventors: James N. Petitte, Samuel Lloyd Pardue
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Patent number: 7993925Abstract: 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.Type: GrantFiled: June 5, 2008Date of Patent: August 9, 2011Assignee: Cold Spring Harbor LaboratoryInventors: Ross Dickins, Scott W. Lowe, Gregory J. Hannon
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Publication number: 20110185439Abstract: The present invention provides GPCR polypeptides and polynucleotides, recombinant materials, and transgenic mice, as well as methods for their production. The polypeptides and polynucleotides are useful, for example, in methods of diagnosis and treatment of diseases and disorders. The invention also provides methods for identifying compounds (e.g., agonists or antagonists) using the GPCR polypeptides and polynucleotides of the invention, and for treating conditions associated with GPCR dysfunction with the GPCR polypeptides, polynucleotides, or identified compounds. The invention also provides diagnostic assays for detecting diseases or disorders associated with inappropriate GPCR activity or levels.Type: ApplicationFiled: December 16, 2010Publication date: July 28, 2011Applicant: OMEROS CORPORATIONInventors: George A. Gaitanaris, John E. Bergmann, Alexander Gragerov, John Hohmann, Fusheng Li, Linda Madisen, Kellie L. McIlwain, Maria N. Pavlova, Demetri Vassilatis, Hongkui Zeng
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Publication number: 20110179510Abstract: A sustained culture of isolated avian gonocytes is provided, as well as a method of making and using the same. A chimeric avian containing an isolated gonocyte and a transgenic avian produced using the chimeric avian are also provided. The cell and method may be employed to make, among other things, transgenic avian that produce a heterologous protein, e.g., a therapeutic protein.Type: ApplicationFiled: January 7, 2011Publication date: July 21, 2011Inventors: Marie-Cecile van de Lavoir, Robert Etches