Involving General Or Homologous Recombination (e.g., Gene Targeting, Etc.) Patents (Class 435/463)
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Patent number: 8088622Abstract: The expansion of a population of stem cells or progenitor cells, or precursors thereof, may be accomplished by disrupting or inhibiting p21cip1/waf1 and/or p27, cyclin dependent kinase inhibitors. In the absence of p27 activity, progenitor cells move into the cell cycle and proliferate; whereas in the absence of p21 activity, stem cells move into the cell cycle and proliferate without losing their pluripotentiality (i.e., their ability to differentiate into the various cell lines found in the blood stream). Any type of stem cell or progenitor cell, or precursor thereof, including, but not limited to, hematopoietic, gastrointestinal, lung, neural, skin, muscle, cardiac muscle, renal, mesenchymal, embryonic, fetal, or liver cell may be used in accordance with the invention.Type: GrantFiled: December 9, 2008Date of Patent: January 3, 2012Assignee: The General Hospital CorporationInventors: David T. Scadden, Tao Cheng
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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: 20110300632Abstract: The present disclosure relates to a method of directing the evolution of an organism by modifying the mutation rate of an organism. The increase in genetic diversity may be used to facilitate the selection of a desired hereditary trait in an organism.Type: ApplicationFiled: August 2, 2011Publication date: December 8, 2011Applicant: NEO-MORGAN LABORATORY INCORPORATEDInventors: Masanori Ogawa, Takayuki Horiuchi, Kazufumi Tabata, Shuntaro Yano, Michi Kubota, Eri Kurita, Akiko Itadani
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Publication number: 20110281361Abstract: Disclosed herein are linear donor molecules comprising homology arms of 50-750 base pairs (e.g., 50-100 base pairs) flanking one or more sequences of interest. The donor molecules and/or compositions comprising these molecules can be used in methods for integration of an exogenous sequence into a specified region of interest in the genome of a cell.Type: ApplicationFiled: June 16, 2011Publication date: November 17, 2011Inventors: Russell DeKelver, Philip D. Gregory, Michael C. Holmes, Fyodor Urnov
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Patent number: 8058505Abstract: A cytoplasmic male sterile cybrid plant of the genus Lactuca, a progeny thereof, or a part thereof having a gene derived from the mitochondria of a plant of the genus Helianthus in its cytoplasm and methods of producing first filial generation seeds using such a cybrid plant.Type: GrantFiled: October 20, 2006Date of Patent: November 15, 2011Assignee: Sakata Seed CorporationInventor: Shingo Horiuchi
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Patent number: 8030538Abstract: The present invention relates to a bovine beta-casein gene targeting vector comprising (1) a first region having a length of 5 to 12 kb which is homologous to the promoter and its flanking nucleic acid sequences of bovine beta-casein gene, and comprising exon 1, intron 1, and exon 2 of bovine beta-casein gene; (2) a region for cloning a nucleic acid coding for desired proteins; (3) a region for coding a positive selection marker; (4) a second region having a length of 2.8 to 3.5 kb which is homologous to the nucleic acid sequences of bovine beta-casein gene, and comprising exon 5, 6, 7 and 8, and intron 5, 6 and 7 of bovine beta-casein gene; wherein the nucleic acid segment corresponding to the first region is located upstream to the nucleic acid segment corresponding to the second region in the 5?-3? arrangement of beta-casein gene.Type: GrantFiled: November 18, 2005Date of Patent: October 4, 2011Assignee: Korea Research Institute of Bioscience and BiotechnologyInventors: Yong-Mahn Han, Kyung-Kwang Lee, Mira Chang, Deog-Bon Koo
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Patent number: 8026052Abstract: The present invention relates to genetic engineering and especially to the use of DNA transposition complex of bacteriophage Mu. In particular, the invention provides a gene transfer system for eukaryotic cells, wherein in vitro assembled Mu transposition complexes are introduced into a target cell and subsequently transposition into a cellular nucleic acid occurs. The invention further provides a kit for producing insertional mutations into the genomes of eukaryotic cells. The kit can be used, e.g., to generate insertional mutant libraries.Type: GrantFiled: April 14, 2004Date of Patent: September 27, 2011Assignee: Finnzymes OyInventors: Harri Savilahti, Mikko Frilander, Xiaojuan Meng, Anja Paatero, Maria Pajunen, Hilkka Turakainen
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Patent number: 8026098Abstract: The invention relates to a process for the removal of selectable marker gene sequences, in particular antibiotic gene sequences, from nucleic acid molecules. The invention further relates to the application of this process in the unlabelled integration and deletion of chromosomal genes and in controlling gene expression.Type: GrantFiled: July 1, 2005Date of Patent: September 27, 2011Assignee: Cobra Biologics LimitedInventors: Rocky Marc Cranenburgh, Alexandra Elizabeth Bloor
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Publication number: 20110190152Abstract: A method for controlling the pluripotent phenotype of a cell comprising modulating the expression or activity of a ESET/SETDB1 polypeptide, or a homologue thereof, within the cell is provided. Pluripotent cells, cultures of such cells and methods for reprogramming somatic cells to a pluripotent phenotype comprising expressing a ESET/SETDB1 polypeptide in the cells, either alone or in combination with other pluripotency factors, are further provided. Methods for identifying modulators of pluripotency and their use in treating cancer or cancer stem cells are also provided.Type: ApplicationFiled: June 4, 2009Publication date: August 4, 2011Inventors: Leng-Siew Yeap, Katsuhiko Hayashi, Azim Surani
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Patent number: 7972854Abstract: 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.Type: GrantFiled: February 3, 2005Date of Patent: July 5, 2011Assignee: Sangamo Biosciences, Inc.Inventors: Jeffrey C. Miller, Lei Zhang
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Patent number: 7972856Abstract: This invention provides methods for obtaining targeted gene modification in vertebrate cells using parvoviral vectors, including adeno-associated virus (AAV). The parvoviral vectors used in the methods of the invention are capable of targeting a specific genetic modification to a preselected target locus in a cellular genome by homologous pairing.Type: GrantFiled: April 24, 2003Date of Patent: July 5, 2011Assignee: The University of WashingtonInventors: David W. Russell, Roli K. Hirata
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Patent number: 7968334Abstract: Methods and compositions for generating novel nucleic acid molecules through targeted spliceosome mediated RNA trans-splicing that result in expression of a apoAI protein, an apoAI variant, the preferred embodiment referred to herein as the apoAI Milano variant, a pre-pro-apoAI or an analogue of apoAI. The methods and compositions include pre-trans-splicing molecules (PTMs) designed to interact with a target precursor messenger RNA molecule (target pre-mRNA) and mediate a trans-splicing reaction resulting in the generation of a novel chimeric RNA molecule (chimeric RNA) capable of encoding apoAI, the apoAI Milano variant, or an analogue of apoAI. The expression of this apoAI protein results in protection against vascular disorders resulting from plaque build up, i.e., atherosclerosis, strokes and heart attacks.Type: GrantFiled: May 31, 2005Date of Patent: June 28, 2011Assignee: VIRxSYS CorporationInventors: Madaiah Puttaraju, Edward Otto, Mariano A. Garcia-Blanco, Gerard J. McGarrity, Gary F. Temple
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Patent number: 7947501Abstract: A method of creating a human pluripotent transgenic stem cell, wherein heterologous DNA is inserted into specific “hot-spots” in the genome where stable and high gene expression may occur, is disclosed. In one embodiment, the method comprises the steps of: (a) selecting a pluripotent stem cell line, and (b) inserting heterologous DNA at an insertion site selected from the group consisting of insertion site one and insertion site two to form a transgenic cell line. In another embodiment, the heterologous DNA is an exchange cassette and the transgenic cell line formed is a master cell line.Type: GrantFiled: February 6, 2009Date of Patent: May 24, 2011Assignee: Wisconsin Alumni Research FoundationInventors: Su-Chun Zhang, Zhong-wei Du
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Publication number: 20110119779Abstract: The invention provides methods and compositions for generating non-human transgenic cells and organisms that are transgenic at one or more gene sequences by separately recombining fragments of a complete gene in temporal sequence. According to the methods of the invention, a set of DNA constructs containing a non-endogenous DNA sequence flanked and/or operably linked at its ends by sequences from the non-human organism are generated by recombination in a bacterial cell, for example, in E. coli. The DNA constructs that are produced can then be introduced into a non-human homologous recombination competent cell where successive cells will contain recombined segments of a target gene, with the ultimate cell in a line containing an endogenous target gene completely replaced by genomic DNA of another species.Type: ApplicationFiled: December 10, 2008Publication date: May 19, 2011Applicant: ALIVA BIOPHARMACEUTICALS, INC.Inventors: Hiroaki Shizuya, Manish Singh, Cecilia Roh
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Publication number: 20110097804Abstract: This invention provides methods for obtaining targeted gene modification in vertebrate cells using parvoviral vectors, including adeno-associated virus (AAV). The parvoviral vectors used in the methods of the invention are capable of targeting a specific genetic modification to a preselected target locus in a cellular genome by homologous pairing.Type: ApplicationFiled: April 24, 2003Publication date: April 28, 2011Inventors: David W. Russell, Roli K. Hirata
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Patent number: 7919679Abstract: 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: October 31, 2007Date of Patent: April 5, 2011Assignee: Monsanto Technology LLCInventor: Larry A. Gilbertson
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Patent number: 7914796Abstract: Disclosed herein are engineered cleavage half-domains; fusion polypeptides comprising these engineered cleavage half-domains; polynucleotides encoding the engineered cleavage half-domains and fusion proteins; and cells comprising these polynucleotides and/or fusion proteins. Also described are methods of using these polypeptides and polynucleotides, for example for targeted cleavage of a genomic sequence.Type: GrantFiled: July 2, 2008Date of Patent: March 29, 2011Assignee: Sangamo Biosciences, Inc.Inventors: Jeffrey C. Miller, Michael C. Holmes, Gregory J. Cost
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Patent number: 7892822Abstract: Recombinant vectors containing infectious viral genomic sequences as well as sequences of a cloning vehicle, a cell comprising the vector, a method for producing the vectors, a method of mutagenizing an infectious viral genomic sequence in the vector, and a vector obtained by the method.Type: GrantFiled: July 31, 1998Date of Patent: February 22, 2011Inventors: Ulrich H. Koszinowski, Martin Messerle, Wolfram Brune, Gabriele Hahn
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Patent number: 7888121Abstract: 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: August 6, 2004Date of Patent: February 15, 2011Assignee: Sangamo Biosciences, Inc.Inventors: Fyodor Urnov, Michael C. Holmes, Jeffrey C. Miller, Carl O. Pabo
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Patent number: 7883720Abstract: 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: July 7, 2004Date of Patent: February 8, 2011Assignee: Wisconsin Alumni Research FoundationInventors: David M. Lynn, Adam D. Miller
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Patent number: 7883890Abstract: Genetically modified mammalian cells comprising a Tol2 transposon transferred into a chromosome can be obtained by co-transfecting mammalian cells with a Tol2 transposase encoded by a Tol2 transposon found in medaka fish, and a Tol2 transposon lacking this transposase.Type: GrantFiled: February 14, 2003Date of Patent: February 8, 2011Assignee: Research Organization of Information and SystemsInventors: Koichi Kawakami, Tetsuo Noda
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Publication number: 20110008895Abstract: The invention lies in the field of production of recombinant gene products in eukaryotic cells. The invention refers to methods and materials for the fast and reproducible generation of production cells lines suitable for large scale production of recombinant gene products. The invention encompasses specific vector systems, genetic engineered host-cells and methods of use.Type: ApplicationFiled: March 27, 2009Publication date: January 13, 2011Applicant: CELONIC AGInventors: Andreas Herrmann, Harry Abts, Benedikt Greulich
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Patent number: 7838295Abstract: 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: October 31, 2007Date of Patent: November 23, 2010Assignee: Monsanto Technology LLCInventor: Larry A. Gilbertson
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Patent number: 7820442Abstract: The present invention identifies that the expression of Activation Induced Deaminase (AID) or its homologues in cells confers a mutator phenotype and thus provides a method for generating diversity in a gene or gene product as well as cell lines capable of generating diversity in defined gene products. The invention also provides methods of modulating a mutator phenotype by modulating AID expression or activity.Type: GrantFiled: November 10, 2004Date of Patent: October 26, 2010Assignee: Medical Research CouncilInventors: Svend K. Petersen-Mahrt, Reuben Harris, Michael Samuel Neuberger, Rupert Christopher Landsdowne Beale
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Publication number: 20100267093Abstract: Disclosed herein are methods for generating recombinant DNA molecules in cells using homologous recombination mediated by recombinases and similar proteins. The methods promote high efficiency homologous recombination in bacterial cells, and in eukaryotic cells such as mammalian cells. The methods are useful for cloning, the generation of transgenic and knockout animals, and gene replacement. The methods are also useful for subcloning large DNA fragments without the need for restriction enzymes. The methods are also useful for repairing single or multiple base mutations to wild type or creating specific mutations in the genome. Also disclosed are bacterial strains and vectors which are useful for high-efficiency homologous recombination.Type: ApplicationFiled: April 14, 2010Publication date: October 21, 2010Inventors: Donald L. Court, Daiguan Yu, E-Chiang Lee, Hilary M. Ellis, Nancy A. Jenkins, Pentao Liu, Neal G. Copeland
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Patent number: 7803991Abstract: The invention provides universal chloroplast integration and expression vectors which are competent to stably transform and integrate genes of interest into chloroplast genome of multiple species of plants. Transformed plants and their progeny are provided. Monocotyledonous and dicotyledonous plants are transformed which have never been transformed heretofore. Plants transformed with a synthetic gene express valuable biodegradable protein-based polymers (PBPs). Transformed plants produce high value molecules. Resistance is provided to agricultural crops against the major classes of chemical herbicides. Herbicide resistance is used as a lethal selectable marker for chloroplast transformation. The transformed plants are capable of expressing in addition to the targeted trait, a desirable, secondary non-targeted trait. Insect resistance is provided to transformed plants, both against insects that are susceptible to Bt toxins and against insects that have developed resistance to Bt toxins.Type: GrantFiled: April 24, 2006Date of Patent: September 28, 2010Assignee: Auburn UniversityInventor: Henry Daniell
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Publication number: 20100229253Abstract: Isolated DNAs encoding the enzyme I-Spoml and its recognition and cutting site are provided. The DNA sequences can be incorporated in cloning and expression vectors, transformed cell lines and transgenic animals. The vectors are useful in gene mapping and site-directed insertion of genes.Type: ApplicationFiled: January 19, 2010Publication date: September 9, 2010Inventors: Stefan Pellenz, Bernard Dujon, Alexis Harington, Bernd Schafer
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Publication number: 20100218264Abstract: Disclosed herein are methods and compositions for genome editing of one or more loci in a rat, 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: December 3, 2009Publication date: August 26, 2010Inventors: Xiaoxia Cui, Aron M. Geurts, Fyodor Urnov
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Patent number: 7776599Abstract: The present invention provides a novel method for obtaining diverse antibodies as a result of markedly enhancing the somatic homologous recombination at an antibody locus in immunocytes. By putting immunocytes in which DNA homologous recombination is occurring at an antibody locus (for example, DT40 cells and the like) into contact and the like with histone acetylase inhibitor and the like (for example, trichostatin A and the like), thereby relaxing the chromatin structure at said antibody locus, somatic homologous recombination at an antibody locus is enhanced, and the production of diverse antibody molecules is made possible. The production of antibodies that bind specifically to antigens from cell populations in which the antibody molecules have been diversified by the enhancement of somatic homologous recombination is made possible by using an appropriate selection method (for example, beads coated with antigen and the like).Type: GrantFiled: July 28, 2003Date of Patent: August 17, 2010Assignees: Riken, Japan Science and Technology AgencyInventors: Kunihiro Ohta, Hidetaka Seo, Takehiko Shibata
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Publication number: 20100197023Abstract: Methods and compositions for performing RNA interference comprising a wide variety of stabilized siRNAs suitable for use in serum-containing media and for in vivo applications, such as therapeutic applications, are provided. These siRNAs permit effective and efficient applications of RNA interference to applications such as diagnostics and therapeutics through the use of one or more modifications including orthoesters, terminal conjugates, modified linkages and 2? modified nucleotides. Uniquely modified siRNAs have been developed that reduces off-target effects incurred in gene-silencing. The modifications include phosphorylation of the first 5? terminal antisense nucleotide; 2? carbon modifications of the first and second or first, second, and third 5? terminal antisense nucleotides; and optionally 2? carbon modifications of the first and second or first, second, and third 5? terminal sense nucleotide. Control and exaequo molecules are also provided.Type: ApplicationFiled: November 25, 2009Publication date: August 5, 2010Applicant: DHARMACON INC.Inventors: Devin Leake, Angela Reynolds, Anastasia Khvorova, William Marshall, Yuriy Fedorov, Kimberly Nichols
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Publication number: 20100172882Abstract: Compositions for targeted mutagenesis of cell surface receptors for HIV and methods of their use are provided herein. The compositions include triplex-forming molecules that bind to duplex DNA in a sequence specific manner at target sites to form triple-stranded structures. The triplex-forming molecules can be triplex-forming oligonucleotides (TFOs) or peptide nucleic acids (PNAs). The triplex-forming molecules are useful to induce site-specific homologous recombination in mammalian cells when used in combination with donor oligonucleotides. The triplex-forming molecules target sites within or adjacent to genes that encodes cell surface receptors for human immunodeficiency virus (HIV). This binding stimulates homologous recombination of a donor oligonucleotide to cause mutations in HIV cell surface receptor genes that result in one or more deficiencies in the ability of the encoded receptor to bind to HIV and allow its transport into the cell.Type: ApplicationFiled: January 11, 2008Publication date: July 8, 2010Inventors: Peter M. Glazer, Ranjit Bindra, Erica B. Schleifman
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Publication number: 20100172976Abstract: A therapeutic composition for inhibiting the function of a target polynucleotide sequence in a mammalian cell includes an agent that provides to a mammalian cell an at least partially double-stranded RNA molecule comprising a polynucleotide sequence of at least about 200 nucleotides in length, said polynucleotide sequence being substantially homologous to a target polynucleotide sequence. This RNA molecule desirably does not produce a functional protein. The agents useful in the composition can be RNA molecules made by enzymatic synthetic methods or chemical synthetic methods in vitro; or made in recombinant cultures of microorganisms and isolated therefrom, or alternatively, can be capable of generating the desired RNA molecule in vivo after delivery to the mammalian cell.Type: ApplicationFiled: December 18, 2009Publication date: July 8, 2010Applicant: ALNYLAM PHARMACEUTICALS, INC.Inventors: Chandrasekhar Satishchandran, Catherine J. Pachuk
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Patent number: 7741077Abstract: The present invention generally relates to the fields of genetic engineering and antibody production. In particular, it relates to the generation of genetically modified vertebrate precursor lymphocytes that have the potential to differentiate into more mature lymphoid lineage cells, and to the use thereof for the production of any heterologous antibody or binding protein.Type: GrantFiled: December 22, 2001Date of Patent: June 22, 2010Assignee: 4-Antibody AGInventors: Ulf Grawunder, Georg Friedrich Melchers
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Publication number: 20100150875Abstract: Cell culture conditions for the isolation, maintenance, and indefinite expansion of human glia are established favoring the growth of neural precursor cells. Cultured cells proliferate indefinitely, express catalytic telomerase, and retain a non-immortalized phenotype. Compositions allow for the indefinite expansion of non-immortalized neural tissue for bioassay applications and restorative neuroscience.Type: ApplicationFiled: November 21, 2005Publication date: June 17, 2010Applicant: University of Florida Research Foundation, Inc.Inventors: Dennis A. Steindler, Noah M. Walton
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Patent number: 7736886Abstract: The invention relates to recombination systems and methods for eliminating nucleic acid sequences from the chromosomal DNA of eukaryotic organisms, and to transgenic organisms—preferably plants—which comprise these systems or were generated using these methods.Type: GrantFiled: January 5, 2004Date of Patent: June 15, 2010Assignee: SunGene GmbH & Co. KGaA and Institut f. Pflanzengenetik u. KulturpflanzenforschungInventors: Holger Puchta, Christian Biesgen
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Patent number: 7700328Abstract: An enteric bacterial strain was engineered to over-produce L-tyrosine using a one-step method. The pheA-tyrA chromosomal region of the bacterial genome was replaced with an engineered chromosomal segment, resulting in inactivation of the pheA coding region and strong expression of the tyrA coding region, resulting in high levels of L-tyrosine production.Type: GrantFiled: June 7, 2006Date of Patent: April 20, 2010Assignee: E.I. du Pont de Nemours and CompanyInventors: Anthony A. Gatenby, Ranjan Patnaik, Fateme Sima Sariaslani, Wonchul Suh, Tina K. Van Dyk
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Publication number: 20100058490Abstract: Methods and means are provided to modulate gene silencing in eukaryotes through the alteration of the functional level of particular DICER or DICER like proteins. Also provided are methods and means to modulate post-transcriptional gene silencing in eukaryotes through the alteration of the functional level of proteins involved in transcriptional silencing of the silencing RNA encoding genes.Type: ApplicationFiled: May 3, 2007Publication date: March 4, 2010Applicant: COMMONWEALTH SCHIENTIFIC AND INDUSTRIAL RESEARCH ORGANIZATIONInventors: Peter Waterhouse, Ming-Bo Wang
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Publication number: 20100048671Abstract: The present invention relates to a newly discovered 44 kD isoform of Pim-1 kinase made in human cells, and to the gene and messenger RNA for the 44 kilodalton isoform. The invention further describes methods and compounds for treating, especially prostate and hematopoietic cancer, by inhibiting expression of the 44 kD isoform of Pim-1 kinase, or its ability to phosphorylate Etk kinase and breast cancer resistance protein (BCRP).Type: ApplicationFiled: May 12, 2006Publication date: February 25, 2010Inventors: Yun Qiu, Kexin Xu, Yingqiu Xie
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Publication number: 20100041738Abstract: A Z-shaped construct having the capacity to hybridize to double stranded DNA in a trans fashion to affect transcription is produced from at least two oligonucleotides, connected to each other, wherein the oligonucleotides are connected to one another through one of sequence specific Watson-Crick base pairing; a covalent linker or a covalent bond directly between the backbones or the bases of said oligonucleotides; or a non-covalent linker or a non-covalent bond directly between the backbones or the bases of said oligonucleotides.Type: ApplicationFiled: June 20, 2006Publication date: February 18, 2010Applicant: AVARIS ABInventors: Edvard Smith, Mathias Svahn, Rongbin Ge
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Publication number: 20100022006Abstract: Regulatory elements, specifically insulators and transgene constructs containing insulator nucleic acid sequences, are disclosed herein. Methods of using insulators and transgene constructs including insulators to inhibit, delay, or prevent gene silencing are also disclosed herein.Type: ApplicationFiled: February 15, 2008Publication date: January 28, 2010Applicant: THE GOVT. OF THE USA AS REPRESENTED BY THE SECRETAInventors: Jung-Hyun Kim, Vladimir L. Larionov, Tom Ebersole
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Publication number: 20100011455Abstract: The invention provides a method for generating a transgenic eukaryotic cell population having a modified human Rosa26 locus, which method includes introducing a functional DNA sequence into the human Rosa26 locus of starting eukaryotic cells. Also provided are targeting vectors useful in the method, as well as a cell population and a transgenic non-human animal comprising a modified human Rosa26 locus. Finally, the invention provides an isolated DNA sequence corresponding to the human Rosa26 locus.Type: ApplicationFiled: January 18, 2008Publication date: January 14, 2010Applicant: Mount Sinai School of Medicine of New York UniversInventors: Gordon Keller, Stefan Irion, Herve Luche, Paul Gadue, Hans Joerg Fehling
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Publication number: 20100009451Abstract: The present invention provides methods modified oligonucleotides and methods of using the modified oligonucleotides for silencing nucleic acids, wherein the nonspecific effects of nucleic acid silencing are reduced.Type: ApplicationFiled: May 29, 2009Publication date: January 14, 2010Applicant: SIGMA ALDRICH COMPANYInventors: Erik R. Eastlund, Greg D. Davis, Derek K. Douglas, David K. Stone
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Patent number: 7642404Abstract: 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: March 21, 2003Date of Patent: January 5, 2010Assignee: ICON Genetics GmbHInventors: Stefan Werner, Anatoly Giritch, Serik Eliby, Sylvestre Marillonnet, Victor Klimyuk, Yuri Gleba
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Publication number: 20090324546Abstract: The invention relates to nucleic acid modifications for a directed expression modulation by the targeted insertion or removal of CpG dinucleotides. The invention also relates to modified nucleic acids and expression vectors.Type: ApplicationFiled: August 3, 2005Publication date: December 31, 2009Inventors: Frank D. Notka, Marcus Graf, Doris Leikam, Ralf Wagner, David Raab
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Patent number: 7638334Abstract: Inhibitors of mismatch repair can be used to generate hypermutable cells and organisms. By inhibiting this process in cells, new cell lines and varieties with novel and useful properties can be prepared more efficiently than by relying on the natural rate of homologous recombination. These methods are useful for generating targeted loci that can alter the expression profiles of target genes as well as tag exons of a gene with a reporter marker to facilitate the monitoring of a given gene product when the host is grown under different conditions or exposed to biological and chemical entities.Type: GrantFiled: January 17, 2003Date of Patent: December 29, 2009Assignee: Morphotek, Inc.Inventors: Nicholas C. Nicolaides, J. Bradford Kline, Luigi Grasso, Philip M. Sass
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Patent number: 7629170Abstract: 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: August 17, 2006Date of Patent: December 8, 2009Assignee: Maxygen, Inc.Inventors: 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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Patent number: 7608752Abstract: The invention provides novel methods of gene targeting using replication in order to increase the efficiency of targeted genetic modification in an eukaryotic organism. Included are vectors, expression cassettes, and modified cells, plants and seeds.Type: GrantFiled: September 20, 2006Date of Patent: October 27, 2009Assignee: Pioneer Hi-Bred International, Inc.Inventors: L. Alexander Lyznik, Xiaoxia Zhao, Isabelle S. Coats, William J. Gordon-Kamm
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Patent number: 7604995Abstract: A method of stimulating homologous recombination by creating at least one nick in a targeted polynucleotide sequence. Wherein nonhomologous recombination is suppressed resulting in increasing the ratio of targeted to nontargeted events. A method of increasing double strand break-initiated gene targeting by inducing a nick in a targeted polynucleotide sequence, wherein overall recombination levels are increased. A method of increasing homologous recombination employing a recombinase that releases the ends in living cells by stimulating homolgous recombination to higher levels than those attainable with standard nucleases. A composition for stimulating homologous recombination including a nicking mechanism for creating nicks in a polynucleotide, wherein the nicking mechanism stimulates homologous recombination. A composition for stimulating homologous recombination including a nicking endonucleases. Various kits for stimulating homologous recombination.Type: GrantFiled: July 9, 2004Date of Patent: October 20, 2009Assignee: New York UniversityInventors: David B. Roth, Gregory S. Lee
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Publication number: 20090258425Abstract: Materials and Methods are provided for target validation by gene knock-down with intracellularly expressed aptamers and siRNAs. The aptamers produced by the materials and methods of the invention are useful in target validation for therapeutics development.Type: ApplicationFiled: June 17, 2009Publication date: October 15, 2009Inventors: David Epstein, Harold Nicholas Marsh, Shannon Pendergrast, Kristin Thompson
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Patent number: 7592502Abstract: A non-human animal that produces human tissue factor (TF) without substantially producing non-human animal tissue factor, said animal having a genome in which cDNA encoding human TF has been inserted upstream of the translation initiation codon for the non-human animal genomic TF gene.Type: GrantFiled: May 17, 2002Date of Patent: September 22, 2009Assignee: Chugai Seiyaku Kabushiki KaishaInventors: Kiyoshi Habu, Kou-ichi Jishage, Hideki Adachi, Naohiro Yabuta