Involving General Or Homologous Recombination (e.g., Gene Targeting, Etc.) Patents (Class 435/463)
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Publication number: 20140193913Abstract: The methods and compositions described herein are based, in part, on the discovery of a stem cell state in human cells that resembles the morphology observed in murine-derived stem cells. Induction of such a state in human stem cells permits an increase in the efficiency of homologous recombination. Thus, the methods and compositions described herein relate to cells and methods for increasing the efficiency of homologous recombination in human stem cells.Type: ApplicationFiled: August 16, 2013Publication date: July 10, 2014Applicant: THE GENERAL HOSPITAL CORPORATIONInventors: Niels Geijsen, Christa Buecker
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Patent number: 8765448Abstract: Methods and means are provided for the exact exchange in eukaryotic cells, such as plant cells, of a target DNA sequence for a DNA sequence of interest through homologous recombination, whereby the selectable or screenable marker used during the homologous recombination phase for temporal selection of the gene replacement events can subsequently be removed without leaving a foot-print employing a method for the removal of a selected DNA flanked by two nucleotide sequences in direct repeats.Type: GrantFiled: June 3, 2008Date of Patent: July 1, 2014Assignee: Bayer Cropscience, N.V.Inventors: Anne Rolland, Manuel Dubald, Michiel Van Lookeren Campagne, Rene Ruiter
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Patent number: 8759105Abstract: 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: June 1, 2007Date of Patent: June 24, 2014Assignee: Regeneron Pharmaceuticals, Inc.Inventors: Aris N. Economides, Andrew J. Murphy, David M. Valenzuela, David Frendewey, George D. Yancopoulos
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Patent number: 8728820Abstract: The invention provides a method for inserting a single stranded replacement nucleic acid into a target nucleic acid, the method comprising the steps of: a) generating a single stranded replacement nucleic acid from a double stranded nucleic acid, wherein the double stranded nucleic acid is adapted at one or both of its 5? ends such that preferential degradation of one strand and/or strand separation generates the single stranded replacement nucleic acid, wherein the single stranded replacement nucleic acid comprises a 5? region that is identical to sequence on the target nucleic acid, a 3? region that is identical to sequence on the target nucleic acid and optionally a replacement region between the 5? and 3? regions that is not identical to sequence on the target nucleic acid, b) exposing the target nucleic acid to the single stranded replacement nucleic acid under conditions suitable for recombination to occur between the single stranded replacement nucleic acid and the target nucleic acid, and c) selectingType: GrantFiled: February 20, 2009Date of Patent: May 20, 2014Assignee: Gene Bridges GmbHInventors: Marcello Maresca, Axel Steffen Erler, Jun Fu, Philipp Martin Seibert, Adrian Francis Stewart, Youming Zhang
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Patent number: 8722964Abstract: This invention relates to the engineering of animal cells, preferably mammalian, more preferably rat, that are deficient due to the disruption of tumor suppressor gene(s) or gene product(s). In another aspect, the invention relates to genetically modified rats, as well as the descendants and ancestors of such animals, which are animal models of human cancer and methods of their use.Type: GrantFiled: April 23, 2010Date of Patent: May 13, 2014Assignee: Transposagen Biopharmaceuticals, Inc.Inventors: Eric M. Ostertag, John Stuart Crawford
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Patent number: 8715972Abstract: Provided is a lactic acid bacterium capable of homolactic fermentation using a pentose as a substrate, the lactic acid bacterium utilizing a pentose, and in which a phosphoketolase pathway is blocked and a pentose phosphate pathway is activated. Also provided is a method for producing lactic acid from a pentose using the lactic acid bacterium and a method for preparing the lactic acid bacterium.Type: GrantFiled: February 15, 2010Date of Patent: May 6, 2014Assignees: Bio-energy Corporation, Kansai Chemical Engineering Co., Ltd.Inventors: Akihiko Kondo, Kenji Okano, Hideo Noda
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Patent number: 8703489Abstract: Disclosed herein are methods and compositions for generating a single-stranded break in a target sequence, which facilitates targeted integration of one or more exogenous sequences.Type: GrantFiled: August 18, 2009Date of Patent: April 22, 2014Assignee: Sangamo BioSciences, Inc.Inventor: Jianbin Wang
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Patent number: 8697851Abstract: 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: December 3, 2012Date of Patent: April 15, 2014Assignee: Regeneron Pharmaceuticals, Inc.Inventors: David Frendewey, David Jonathan Heslin, Ka-Man Venus Lai, David M. Valenzuela
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Patent number: 8669418Abstract: The present invention belongs to the field of functional proteomics and more particularly to the field of protein aggregation. The invention discloses a method for interfering with the function of a target protein and uses a non-naturally, user-designed molecule, designated as interferor, that has a specificity for a target protein and which induces aggregation upon contact with said target protein. The present invention also discloses such interferor molecules and their use in agrobiotech applications.Type: GrantFiled: May 6, 2011Date of Patent: March 11, 2014Assignees: VIB VZW, Vrije Universiteit BrusselInventors: Joost Schymkowitz, Frederic Rousseau
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Patent number: 8658155Abstract: Methods and compositions for producing selected non-human mammalian germ cells and gametes and for making non-human animals using the produced germ cells and gametes are provided by the present invention. Methods of generating a non-human embryo and/or animal derived from donor stem cells, methods of generating chimeric non-human animals having substantially all gametes and/or germ cells derived from the donor stem cells, methods of producing a non-human host embryo lacking functional endogenous germ cells and non-human host embryos incapable of developing endogenous gametes of the present invention are described herein.Type: GrantFiled: December 27, 2011Date of Patent: February 25, 2014Assignee: The Jackson LaboratoryInventors: Michael V. Wiles, Robert Taft
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Patent number: 8604281Abstract: A process of producing transgenic multi-cellular plants or parts thereof expressing a trait of interest that has a controlled distribution of said trait to progeny, comprising (i) producing a first plant or a cell thereof having in a first locus of a nuclear chromosome a first heterologous nucleotide sequence comprising a first fragment of a nucleotide sequence encoding said trait of interest, (ii) producing a second plant or a cell thereof having in a second locus of a nuclear chromosome homologous to said nuclear chromosome of step (i), a second heterologous nucleotide sequence comprising a second fragment of the nucleotide sequence encoding said trait of interest, and (iii) hybridising said first and said second plants or cells thereof to generate progeny exhibiting said functional trait of interest. Also disclosed is a process of producing hybrid seeds for agriculture.Type: GrantFiled: May 14, 2012Date of Patent: December 10, 2013Assignee: Bayer CropScience NVInventors: Stefan Werner, Anatoly Giritch, Serik Eliby, Sylvestre Marillonnet, Victor Klimyuk, Yuri Gleba
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Publication number: 20130316366Abstract: Some embodiments herein provide compositions and methods for expressing secreted and cell-surface-bound polypeptides in a single cell. In some embodiments, secreted and cell-surface polypeptide are produced from a single polynucleotide. The polynucleotide can comprise a sequence (or sequence encoding a polypeptide) that mediates separation of a membrane anchor from the polypeptide. In some embodiments, a desired ratio of secreted to surface-bound polypeptide is obtained by selecting a sequence that mediates a desired level of separation of the membrane anchor from the polypeptide.Type: ApplicationFiled: May 24, 2013Publication date: November 28, 2013Applicant: CALIFORNIA INSTITUTE OF TECHNOLOGYInventors: Kenneth Yu, David Baltimore, Lili Yang
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Publication number: 20130309670Abstract: Compositions and methods are provided for making one or more targeted genetic modifications at a target genomic locus by employing homologous recombination facilitated by single or double-strand break at or near the target genomic locus. Compositions and methods for promoting efficiency of homologous recombination between an LTVEC and a target genomic locus in prokaryotic or eukaryotic cells using engineered nucleases are also provided.Type: ApplicationFiled: April 25, 2013Publication date: November 21, 2013Applicant: Regeneron Pharmaceuticals, Inc.Inventors: David Frendewey, Wojtek Auerbach, David M. Valenzuela, George D. Yancopoulos
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Publication number: 20130295675Abstract: The present invention provides reagents and methods for improved homologous recombination.Type: ApplicationFiled: June 26, 2013Publication date: November 7, 2013Applicants: Arizona StateInventors: Bertram JACOBS, Stacy WHITE, Kip CONWELL, Jeffrey LANGLAND, James JANCOVICH
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Patent number: 8557512Abstract: This invention is directed to a general method for the chronic treatment, potential cure, or prevention of various metabolic and related diseases in people, including diabetes, by modulating IRS2 activity in cells and tissues in the body. IRS1 and IRS2 are part of the insulin or insulin-like growth factor signaling pathway. By upregulating the levels or functional activity of IRS2, insulin is used more efficiently by the body to control nutrient levels. By upregulating IRS2 levels or functional activity in pancreatic ?-cells, glucose sensing and insulin secretion are enhanced.Type: GrantFiled: December 31, 2003Date of Patent: October 15, 2013Assignee: HMI Medical Innovations, LLCInventors: Gerard M. Housey, Morris F. White
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Production of modified fatty acids in plants through rDNA targeted integration of heterologous genes
Patent number: 8546645Abstract: The present invention relates to transgenic plants comprising a plurality of nucleic acids heterologous to said plant, each of said nucleic acid comprising a coding sequence operably linked to one or more regulatory elements for directing expression of said coding sequence in said plant, said nucleic acid being stably integrated at or adjacent to rDNA sequences, or a seed, organ, tissue, part or cell thereof, or a descendant of said plant, seed, organ, tissue, part or cell; methods of producing the transgenic plants; and methods of producing oil using the transgenic plants.Type: GrantFiled: September 30, 2009Date of Patent: October 1, 2013Assignee: Agrisoma Biosciences Inc.Inventors: Steven Fabijanski, Michael Lindenbaum, Ping Fu, Elizabeth-France Marillia -
Patent number: 8541237Abstract: Disclosed herein is a composition for molecular imaging comprising a trans-splicing ribozyme coupled with an imaging reporter gene. The trans-splicing ribozyme targets a specific gene associated with a disease. Also disclosed is a molecular imaging method using the composition.Type: GrantFiled: October 26, 2007Date of Patent: September 24, 2013Assignee: National Cancer CenterInventors: In-Hoo Kim, Seong-Wook Lee, Seung-Hee Hong, Jin-Sook Jeong, Yoon-Jong Lee, Yeon-Su Lee, Haeng-Im Jung
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Publication number: 20130244246Abstract: This invention relates to immortalized avian cells, and to the use of these cells for the production of viruses. The cells according to the invention are particularly useful for the production of recombinant viral vectors which can be used for the preparation of therapeutic and/or prophylactic compositions for the treatment of animals and more particularly humans.Type: ApplicationFiled: December 21, 2012Publication date: September 19, 2013Applicant: TRANSGENE S.A.`Inventors: Philippe Erbs, Marina Kapfer, Nathalie Silvestre
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Patent number: 8524500Abstract: Disclosed herein are methods and compositions for targeted cleavage of a genomic sequence, targeted alteration of a genomic sequence, and targeted recombination between a genomic region and an exogenous polynucleotide homologous to the genomic region. The compositions include fusion proteins comprising a cleavage domain (or cleavage half-domain) and an engineered zinc finger domain and polynucleotides encoding same. Methods for targeted cleavage include introduction of such fusion proteins, or polynucleotides encoding same, into a cell. Methods for targeted recombination additionally include introduction of an exogenous polynucleotide homologous to a genomic region into cells comprising the disclosed fusion proteins.Type: GrantFiled: July 16, 2010Date of Patent: September 3, 2013Assignee: Sangamo BioSciences, Inc.Inventors: Fyodor Urnov, Michael C. Holmes, Jeffrey C. Miller, Carl O. Pabo
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Patent number: 8524368Abstract: The present invention provides dynamic charge state cationic polymers that are useful for delivery of anionic molecules. The dynamic charge state cationic polymers are designed to have cationic charge densities that decrease by removal of removable functional groups from the polymers. The present invention also provides interpolyelectrolyte complexes containing the polymers complexed to a polyanion. Methods for using the interpolyelectrolyte complexes to deliver anionic compounds are also provided.Type: GrantFiled: December 14, 2011Date of Patent: September 3, 2013Assignee: Wisconsin Alumni Research FoundationInventors: David M. Lynn, Adam D. Miller
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Publication number: 20130209437Abstract: A method for engineering I-CreI homing endonuclease variants able to cleave mutant I-CreI sites having variation in positions ±8 to ±10. A I-CreI homing endonuclease variant obtainable by said method, a vector encoding said variant, a cell, an animal or a plant modified by said vector. Use of said I-CreI endonuclease variant and derived products for genetic engineering, genome therapy and antiviral therapy.Type: ApplicationFiled: January 17, 2013Publication date: August 15, 2013Applicant: CELLECTISInventor: Cellectis
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Publication number: 20130212725Abstract: The present invention relates to a method of modifying a target sequence in the genome of a eukaryotic cell, the method comprising the step: (a) introducing into the cell a fusion protein comprising a DNA-binding domain of a Tal effector protein and a non-specific cleavage domain of a restriction nuclease or a nucleic acid molecule encoding the fusion protein in expressible form, wherein the fusion protein specifically binds within the target sequence and introduces a double strand break within the target sequence. The present invention further relates to the method of the invention, wherein the modification of the target sequence is by homologous recombination with a donor nucleic acid sequence further comprising the step: (b) introducing a nucleic acid molecule into the cell, wherein the nucleic acid molecule comprises the donor nucleic acid sequence and regions homologous to the target sequence.Type: ApplicationFiled: June 7, 2011Publication date: August 15, 2013Applicant: HELMHOLTZ ZENTRUM MUNCHEN DEUTSCHES FORSCHUNGSZENTRUM FUR GESUNDHEIT UNDInventors: Ralf Kühn, Wolfgang Wurst, Melanie Meyer
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Patent number: 8476072Abstract: The invention relates to a set of genetic constructs which allow the efficient and reproducible introduction of a specific nucleotide sequence at a fixed position in the genome by generating a double strand break at a specific position in the genome using a meganuclease and so stimulating a homologous recombination event at this locus between the genomic site and a transfected donor sequence. The present invention also relates to methods using these constructs and to these materials in the form of a kit.Type: GrantFiled: October 23, 2009Date of Patent: July 2, 2013Assignee: CellectisInventors: Jean-Pierre Cabaniols, Andre Choulika, Christophe Delenda
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Publication number: 20130130388Abstract: 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: December 19, 2012Publication date: May 23, 2013Applicant: Regeneron Pharmaceuticals, Inc.Inventor: Regeneron Pharmaceuticals, Inc.
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Patent number: 8420884Abstract: Methods for screening compounds to treat an oncological disorder regulated through a tumor-inducing pathway are provided. The compounds are administered to non-human animal subjects having a disease model, so that the subjects display pathology symptoms that correspond to the oncological disorder in humans. The subjects carry a regulatable transgene expression, of which is associated with tumor formation, and further carry regulatable genes for suppression of tumor formation. The disease-pathology symptoms are induced using a site-specific recombination system to induce expression of the transgene associated with tumor formation and negatively regulate or eliminate the genes for suppression of the tumor formation. The methods further involve analyzing tumor formation in subjects administered the compound and comparing appearance and amount of tumors in the subjects administered the compound with control subjects not administered the compound.Type: GrantFiled: October 16, 2009Date of Patent: April 16, 2013Assignee: Tufts Medical Center Inc.Inventor: Alain Charest
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Patent number: 8420782Abstract: The present invention refers to methods for selectively recognizing a base pair in a DNA sequence by a polypeptide, to modified polypeptides which specifically recognize one or more base pairs in a DNA sequence and, to DNA which is modified so that it can be specifically recognized by a polypeptide and to uses of the polypeptide and DNA in specific DNA targeting as well as to methods of modulating expression of target genes in a cell.Type: GrantFiled: January 31, 2012Date of Patent: April 16, 2013Inventors: Ulla Bonas, Jens Boch, Sebastian Schornack, Thomas Lahaye
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Patent number: 8409861Abstract: Disclosed herein are methods and compositions for targeted deletion of double-stranded DNA. The compositions include fusion proteins comprising a cleavage domain (or cleavage half-domain) and an engineered zinc finger domain, and polynucleotides encoding same. Methods for targeted deletion include introduction of such fusion proteins, or polynucleotides encoding same, into a cell such that two targeted cleavage events occur. Subsequent cellular repair mechanisms result in deletion of sequences between the two cleavage sites.Type: GrantFiled: December 15, 2005Date of Patent: April 2, 2013Assignee: Sangamo BioSciences, Inc.Inventors: Dmitry Guschin, Michael C. Holmes
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Patent number: 8377674Abstract: Rationally-designed LAGLIDADG meganucleases and methods of making such meganucleases are provided. In addition, methods are provided for using the meganucleases to generate recombinant cells and organisms having a desired DNA sequence inserted into a limited number of loci within the genome, as well as methods of gene therapy, for treatment of pathogenic infections, and for in vitro applications in diagnostics and research.Type: GrantFiled: June 25, 2012Date of Patent: February 19, 2013Assignee: Duke UniversityInventors: James Jefferson Smith, Derek Jantz, Homme W. Hellinga
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Publication number: 20130040302Abstract: Methods for producing engineered induced pluripotent stem (iPS) cells are provided comprising introducing a first nucleic acid into somatic cells for integration into their genome and reprogramming the cells to produce engineered iPS cells having the nucleic acid integrated into their genome. For example, in certain aspects the cells are reprogrammed by introduction of a genetic element that expresses one or more reprogramming factor and culturing of the cells under conditions sufficient to produce reprogrammed cells.Type: ApplicationFiled: July 11, 2012Publication date: February 14, 2013Inventors: Thomas J. Burke, Michael Miller, Michael McLachlan, Sarah Jane Dickerson, Anne Strouse
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Patent number: 8361751Abstract: A cell in which the activity of a protein relating to transport of an intracellular sugar nucleotide, GDP-fucose, to the Golgi body is more decreased or deleted than its parent cell; a process for producing an antibody composition using the cell; a transgenic non-human animal or plant or the progenies thereof, in which genome is modified so as to have a decreased or deleted activity of a protein relating to transport of an intracellular sugar nucleotide, GDP-fucose, to the Golgi body; a process for producing an antibody composition from the animal or plant; and a medicament comprising the antibody composition.Type: GrantFiled: May 19, 2010Date of Patent: January 29, 2013Assignee: Kyowa Hakko Kirin Co., LtdInventors: Yutaka Kanda, Mitsuo Satoh, Katsuhiro Mori
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Patent number: 8338138Abstract: The invention provides molecular switches which couple external signals to functionality, and combinatorial methods of making and using the same involving circular permutation of nucleic acid and amino acid sequences. The switches according to the invention can be used, for example, to regulate gene transcription, target drug delivery to specific cells, transport drugs intracellularly, control drug release, provide conditionally active proteins, perform metabolic engineering, and modulate cell signaling pathways. Libraries comprising the switches, expression vectors and host cells for expressing the switches are also provided.Type: GrantFiled: January 28, 2005Date of Patent: December 25, 2012Assignee: The John Hopkins UniversityInventors: Marc A. Ostermeier, Gurkan Guntas
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Patent number: 8334428Abstract: Methods and compositions reduce copy number of transgenes and minimizing vector backbone sequences in plant transformation. Agrobacterium strains with T-DNA integrated into the chromosomal DNA of the Agrobacterium reduce the copy number and vector backbone sequences. Chromosomal integration vectors to integrate T-DNA into a specific locus of Agrobacterium chromosome are disclosed.Type: GrantFiled: November 14, 2007Date of Patent: December 18, 2012Assignees: Purdue Research Foundation, Iowa State University Research Foundation, Inc.Inventors: Stanton B. Gelvin, Heiko Oltmanns, Lan Ying Lee, Bronwyn Frame, Kan Wang
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Patent number: 8329986Abstract: Disclosed herein are methods and compositions for targeted integration of an exogenous sequence into a plant Zp15 locus, for example, for expression of a polypeptide of interest.Type: GrantFiled: December 17, 2009Date of Patent: December 11, 2012Assignees: Dow AgroSciences, LLC, Sangamo BioSciences, Inc.Inventors: Holly J. Butler, David R. Corbin, Yannick Doyon, Zhifang Gao, Vipula K. Shukla, Fyodor Urnov, Sarah E. Worden
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Patent number: 8309356Abstract: Compositions and methods for targeted gene therapy are disclosed. Compositions containing double duplex-forming pseudocomplementary oligonucleotides are administered in combination with a donor oligonucleotide that is homologous to a target sequence on a double-stranded DNA molecule in need of repair or replacement. By activating cellular mechanisms involved in DNA synthesis, repair and recombination, the double duplex-forming pseudocomplementary oligonucleotides can introduce one or more mutations at a site of interest by increasing the efficiency of targeted recombination of the donor oligonucleotide. The pseudocomplementary oligonucleotides/donor oligonucleotide compositions may be administered in combination with a second therapeutic agent that enhances access of the pseudocomplementary oligonucleotides and/or the donor oligonucleotide to the target site, an agent that enhances or increases DNA repair or recombination, or an agent that enhances uptake or delivery of the oligonucleotides.Type: GrantFiled: April 1, 2010Date of Patent: November 13, 2012Assignee: Yale UniversityInventor: Peter M. Glazer
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Publication number: 20120282698Abstract: A method to construct eukaryotic cells having a target sequence in a chromosomal DNA sequence replaced by a desired replacement sequence is disclosed.Type: ApplicationFiled: May 11, 2012Publication date: November 8, 2012Applicant: DSM IP ASSETS B.V.Inventors: Marco Alexander van den BERG, Richard KERKMAN, Hesselien TOUW-RIEL
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Publication number: 20120270264Abstract: Disclosed is a DNA construct that is useful for efficient production of recombinant CHO cells useful for the production of target proteins. The DNA construct is a construct comprising, from a 5? end toward a 3? end, a first homologous DNA fragment, a target protein gene, and a second homologous DNA fragment. The first and second homologous DNA fragments have homology allowing for homologous recombination with a part of a hypoxanthine-phosphoribosyltransferase enzyme (hprt) locus in a CHO cell genome and have a chain length of not less than 1 kbp.Type: ApplicationFiled: September 21, 2010Publication date: October 25, 2012Applicant: TOTO LTD.Inventors: Shuji Sonezaki, Yumi Ogami, Yoshimasa Yamana, Junya Narita
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Patent number: 8288160Abstract: The invention is directed to a cell comprising a nucleic acid encoding an Activation Induced Deaminase (AID) polypeptide, a fusion protein comprising an AID polypeptide, and methods of using a nucleic acid encoding an AID polypeptide.Type: GrantFiled: October 25, 2010Date of Patent: October 16, 2012Assignee: Medical Research CouncilInventors: Svend K. Petersen-Mahrt, Reuben Harris, Michael Samuel Neuberger, Rupert Christopher Landsdowne Beale
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Publication number: 20120252123Abstract: The present invention features compositions and methods for introducing, into cells, nucleic acids whose expression results in chromosomal silencing. The nucleic acids are targeted to specific chromosomal regions where they subsequently reduce the expression of deleterious genes, or cause the death of deleterious cells. Where the nucleic acid sequence is a silencing sequence, it may encode an Xist RNA or other non-coding, silencing RNA. Accordingly, the present invention features, inter alia, nucleic acid constructs that include a transgene (e.g., a silencing sequence encoding an Xist RNA or other non-coding RNA that silences a segment of a chromosome); first and second sequences that direct insertion of the silencing sequence into a targeted chromosome; and, optionally, a selectable marker.Type: ApplicationFiled: May 30, 2012Publication date: October 4, 2012Applicant: UNIVERSITY OF MASSACHUSETTSInventors: Jeanne B. Lawrence, Lisa L. Hall
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Patent number: 8247232Abstract: A process to prepare a recombined transgenic Zea mays plant or plant cell from a first transgenic Zea mays plant cell, wherein the transgene in the recombinant plant or plant cell has an altered genetic structure relative to the genetic structure of the transgene in the first transgenic plant cell, due to homologous recombination-mediated transgene deletion.Type: GrantFiled: April 5, 2011Date of Patent: August 21, 2012Assignee: Monsanto Technology LLCInventor: Larry A. Gilbertson
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Patent number: 8232448Abstract: This application is in the field of sialic acid chemistry, metabolism, antigenicity, and the production of transgenic non-human mammals with altered sialic acid production. More particularly, this application relates to N-glycolylneuraminic acid (Neu5Gc) being an immunogen in humans, and the production of Neu5Gc-free mammalian products for laboratory and human use.Type: GrantFiled: June 8, 2006Date of Patent: July 31, 2012Assignee: The Regents of the University of CaliforniaInventors: Ajit Varki, Anna Maria Hedlund, Dzung Nguyen
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Publication number: 20120178169Abstract: Materials and Methods related to gene targeting (e.g., gene targeting with transcription activator-like effector nucleases; “TALENS”) are provided.Type: ApplicationFiled: March 22, 2012Publication date: July 12, 2012Inventors: Daniel F. Voytas, Adam J. Bogdanove, Feng Zhang
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Publication number: 20120142110Abstract: A transgenic cat with a phenotype characterized by the substantial absence of the major cat allergen, Fel d I. The phenotype is conferred in the transgenic cat by disrupting the coding sequence of the target gene with a specialized construct. The phenotype of the transgenic cat is transmissible to its offspring.Type: ApplicationFiled: June 24, 2011Publication date: June 7, 2012Inventors: David B. Avner, Sven Bocklandt, James Kehler
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Patent number: 8193410Abstract: A process of producing a transgenic multi-cellular plants or parts thereof expressing a trait of interest, said trait having a controlled distribution of said trait to progeny, wherein said process comprises (i) producing a first plant or a cell thereof having in a first locus of a nuclear chromosome a first heterologous nucleotide sequence comprising a first fragment of a nucleotide sequence encoding said trait of interest, (ii) producing a second plant or a cell thereof having in a second locus of a nuclear chromosome homologous to said nuclear chromosome of step (i), a second heterologous nucleotide sequence comprising a second fragment of the nucleotide sequence encoding said trait of interest, and (iii) hybridising said first and said second plant or cells thereof to generate progeny exhibiting said functional trait of interest due to binding between a protein or polypeptide encoded by said first heterologous nucleotide sequence and a protein or polypeptide encoded by said second heterologous nucleotideType: GrantFiled: November 19, 2009Date of Patent: June 5, 2012Assignee: Icon Genetics GmbHInventors: Stefan Werner, Anatoly Giritch, Serik Eliby, Sylvestre Marillonnet, Victor Klimyuk, Yuri Gleba
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Patent number: 8158404Abstract: The present invention relates to recombinant microorganisms comprising biosynthetic pathways and methods of using said recombinant microorganisms to produce various beneficial metabolites. In various aspects of the invention, the recombinant microorganisms may further comprise one or more modifications resulting in the reduction or elimination of 3 keto-acid (e.g., acetolactate and 2-aceto-2-hydroxybutyrate) and/or aldehyde-derived by-products. In various embodiments described herein, the recombinant microorganisms may be microorganisms of the Saccharomyces clade, Crabtree-negative yeast microorganisms, Crabtree-positive yeast microorganisms, post-WGD (whole genome duplication) yeast microorganisms, pre-WGD (whole genome duplication) yeast microorganisms, and non-fermenting yeast microorganisms.Type: GrantFiled: March 30, 2011Date of Patent: April 17, 2012Assignee: Gevo, Inc.Inventors: Doug Lies, Stephanie Porter-Scheinman, Julie Kelly, Catherine Asleson Dundon, Aristos Aristidou, Andrew Hawkins
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Patent number: 8153415Abstract: The present invention relates to recombinant microorganisms comprising biosynthetic pathways and methods of using said recombinant microorganisms to produce various beneficial metabolites. In various aspects of the invention, the recombinant microorganisms may further comprise one or more modifications resulting in the reduction or elimination of 3 keto-acid (e.g., acetolactate and 2-aceto-2-hydroxybutyrate) and/or aldehyde-derived by-products. In various embodiments described herein, the recombinant microorganisms may be microorganisms of the Saccharomyces clade, Crabtree-negative yeast microorganisms, Crabtree-positive yeast microorganisms, post-WGD (whole genome duplication) yeast microorganisms, pre-WGD (whole genome duplication) yeast microorganisms, and non-fermenting yeast microorganisms.Type: GrantFiled: March 31, 2011Date of Patent: April 10, 2012Assignee: Gevo, Inc.Inventors: Thomas Buelter, Andrew Hawkins, Stephanie Porter-Scheinman, Peter Meinhold, Catherine Asleson Dundon, Aristos Aristidou, Jun Urano, Doug Lies, Matthew Peters, Melissa Dey, Justas Jancauskas, Julie Kelly, Ruth Berry
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Patent number: 8143480Abstract: This invention relates to methods for knock-down of a target gene in plants, particularly efficient and specific methods for knock-down of a target gene in plants. This invention also relates to methods for silencing endogenous plant genes or plant pathogen genes. It further relates to nucleic acid constructs (DNA, RNA) which comprise a nucleic acid sequence that corresponds to a target gene or fragment thereof flanked by two complementary sites to an smRNA, e.g., a miRNA (one complementary site is on either side of the nucleic acid sequence), resulting in, for example the configuration: complementary site—nucleic acid sequence that corresponds to a target gene—complementary site.Type: GrantFiled: October 19, 2007Date of Patent: March 27, 2012Assignee: Whitehead Institute for Biomedical ResearchInventors: Michael Axtell, David P. Bartel
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Patent number: 8133715Abstract: The present invention relates to recombinant microorganisms comprising biosynthetic pathways and methods of using said recombinant microorganisms to produce various beneficial metabolites. In various aspects of the invention, the recombinant microorganisms may further comprise one or more modifications resulting in the reduction or elimination of 3 keto-acid (e.g., acetolactate and 2-aceto-2-hydroxybutyrate) and/or aldehyde-derived by-products. In various embodiments described herein, the recombinant microorganisms may be microorganisms of the Saccharomyces clade, Crabtree-negative yeast microorganisms, Crabtree-positive yeast microorganisms, post-WGD (whole genome duplication) yeast microorganisms, pre-WGD (whole genome duplication) yeast microorganisms, and non-fermenting yeast microorganisms.Type: GrantFiled: March 29, 2011Date of Patent: March 13, 2012Assignee: Gevo, Inc.Inventors: Thomas Buelter, Andrew Hawkins, Stephanie Porter-Scheinman, Peter Meinhold, Catherine Asleson Dundon, Aristos Aristidou, Jun Urano, Matthew Peters, Melissa Dey, Justas Jancauskas, Julie Kelly, Ruth Berry
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Patent number: 8105831Abstract: The present invention provides methods of generating a mammalian cell that is homozygous at a locus of interest, as well as cells made by the method. The present invention further provides methods of using the cells.Type: GrantFiled: March 7, 2008Date of Patent: January 31, 2012Assignee: University of WashingtonInventors: David W. Russell, Roli K. Hirata
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Patent number: 8097277Abstract: The present invention provides dynamic charge state cationic polymers that are useful for delivery of anionic molecules. The dynamic charge state cationic polymers are designed to have cationic charge densities that decrease by removal of removable functional groups from the polymers. The present invention also provides interpolyelectrolyte complexes containing the polymers complexed to a polyanion. Methods for using the interpolyelectrolyte complexes to deliver anionic compounds are also provided.Type: GrantFiled: November 19, 2010Date of Patent: January 17, 2012Assignee: Wisconsin Alumni Research FoundationInventors: David M. Lynn, Adam D. Miller
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Patent number: 8097460Abstract: The present invention relates to the production of ethanol as a product of bacterial fermentation. In particular this invention relates to a novel method of gene inactivation and gene expression based upon homologous recombination. The method is particularly useful in connection with species of Bacillus such as B. stereothermophilus, B. calvodelox, B. caldotenax, B. thermoglucosidasius, B. coagulans, B. licheniformis, B. thermodenitrificans, and B. caldolyticus.Type: GrantFiled: February 24, 2009Date of Patent: January 17, 2012Assignee: Elsworth Biotechnology LimitedInventors: Muhammed Javed, Fiona Cusdin, Paul Milner, Edward Green