JP4063326B2 - 非天然ヌクレオチドを有するキメラ突然変異性ベクター - Google Patents
非天然ヌクレオチドを有するキメラ突然変異性ベクター Download PDFInfo
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- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/82—Vectors or expression systems specially adapted for eukaryotic hosts for plant cells, e.g. plant artificial chromosomes (PACs)
- C12N15/8201—Methods for introducing genetic material into plant cells, e.g. DNA, RNA, stable or transient incorporation, tissue culture methods adapted for transformation
- C12N15/8213—Targeted insertion of genes into the plant genome by homologous recombination
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- C12N15/09—Recombinant DNA-technology
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- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/82—Vectors or expression systems specially adapted for eukaryotic hosts for plant cells, e.g. plant artificial chromosomes (PACs)
- C12N15/8241—Phenotypically and genetically modified plants via recombinant DNA technology
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- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
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- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
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- C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
- C12N15/90—Stable introduction of foreign DNA into chromosome
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- C12P19/00—Preparation of compounds containing saccharide radicals
- C12P19/26—Preparation of nitrogen-containing carbohydrates
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- C12P19/30—Nucleotides
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- C12N2800/00—Nucleic acids vectors
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- General Chemical & Material Sciences (AREA)
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Applications Claiming Priority (3)
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| US08/664,487 US5731181A (en) | 1996-06-17 | 1996-06-17 | Chimeric mutational vectors having non-natural nucleotides |
| US08/664,487 | 1996-06-17 | ||
| PCT/US1997/010538 WO1997048714A1 (en) | 1996-06-17 | 1997-06-16 | Chimeric mutational vectors having non-natural nucleotides |
Publications (3)
| Publication Number | Publication Date |
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| JP2000512853A JP2000512853A (ja) | 2000-10-03 |
| JP2000512853A5 JP2000512853A5 (OSRAM) | 2004-12-09 |
| JP4063326B2 true JP4063326B2 (ja) | 2008-03-19 |
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| JP50328298A Expired - Fee Related JP4063326B2 (ja) | 1996-06-17 | 1997-06-16 | 非天然ヌクレオチドを有するキメラ突然変異性ベクター |
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| Country | Link |
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| US (2) | US5731181A (OSRAM) |
| EP (1) | EP0968224A4 (OSRAM) |
| JP (1) | JP4063326B2 (OSRAM) |
| KR (1) | KR20000011075A (OSRAM) |
| AU (1) | AU732417B2 (OSRAM) |
| CA (1) | CA2258090A1 (OSRAM) |
| NZ (1) | NZ333201A (OSRAM) |
| WO (1) | WO1997048714A1 (OSRAM) |
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| US6524613B1 (en) | 1997-04-30 | 2003-02-25 | Regents Of The University Of Minnesota | Hepatocellular chimeraplasty |
| GB9711015D0 (en) * | 1997-05-28 | 1997-07-23 | Zeneca Ltd | Improvements in or relating to organic compounds |
| KR20010022652A (ko) * | 1997-08-05 | 2001-03-26 | 키메라젠, 인크. | 식물에서 국소적인 유전자변형을 유발하기 위한 혼성 이중나선올리고뉴클레오티드의 용도 |
| US6348450B1 (en) | 1997-08-13 | 2002-02-19 | The Uab Research Foundation | Noninvasive genetic immunization, expression products therefrom and uses thereof |
| US6716823B1 (en) | 1997-08-13 | 2004-04-06 | The Uab Research Foundation | Noninvasive genetic immunization, expression products therefrom, and uses thereof |
| US20030045492A1 (en) * | 1997-08-13 | 2003-03-06 | Tang De-Chu C. | Vaccination by topical application of recombinant vectors |
| US20030125278A1 (en) * | 1997-08-13 | 2003-07-03 | Tang De-Chu C. | Immunization of animals by topical applications of a salmonella-based vector |
| US6706693B1 (en) | 1997-08-13 | 2004-03-16 | The Uab Research Foundation | Vaccination by topical application of genetic vectors |
| AU760113C (en) | 1997-11-18 | 2004-04-22 | Pioneer Hi-Bred International, Inc. | Compositions and methods for genetic modification of plants |
| AU1526199A (en) | 1997-11-18 | 1999-06-07 | Pioneer Hi-Bred International, Inc. | Targeted manipulation of herbicide-resistance genes in plants |
| US7102055B1 (en) | 1997-11-18 | 2006-09-05 | Pioneer Hi-Bred International, Inc. | Compositions and methods for the targeted insertion of a nucleotide sequence of interest into the genome of a plant |
| US6010907A (en) | 1998-05-12 | 2000-01-04 | Kimeragen, Inc. | Eukaryotic use of non-chimeric mutational vectors |
| US6004804A (en) * | 1998-05-12 | 1999-12-21 | Kimeragen, Inc. | Non-chimeric mutational vectors |
| US6150105A (en) * | 1998-08-20 | 2000-11-21 | Genetic Assays, Inc. | Methods of screening nucleic acids for nucleotide variations |
| DE19956568A1 (de) * | 1999-01-30 | 2000-08-17 | Roland Kreutzer | Verfahren und Medikament zur Hemmung der Expression eines vorgegebenen Gens |
| AU2008202208C1 (en) * | 1999-01-30 | 2014-04-24 | Alnylam Pharmaceuticals, Inc. | Method and medicament for inhibiting the expression of a defined gene |
| ATE529130T1 (de) * | 1999-04-08 | 2011-11-15 | Intercell Usa Inc | Trockenformulierung für transkutane immunisierung |
| US6348050B1 (en) * | 1999-04-30 | 2002-02-19 | Medtronic, Inc. | Infusion systems for creating microenvironments in a living body |
| US20040009936A1 (en) * | 1999-05-03 | 2004-01-15 | Tang De-Chu C. | Vaccine and drug delivery by topical application of vectors and vector extracts |
| CA2373748A1 (en) * | 1999-05-21 | 2000-11-30 | The University Of Miami | Use of chimeric mutational vectors to change endogenous nucleotide sequences in solid tissues |
| US6271360B1 (en) | 1999-08-27 | 2001-08-07 | Valigen (Us), Inc. | Single-stranded oligodeoxynucleotide mutational vectors |
| CA2389441A1 (en) * | 1999-10-07 | 2001-04-12 | Valigen, Inc. | Compositions and methods for plant genetic modification |
| AR025996A1 (es) | 1999-10-07 | 2002-12-26 | Valigen Us Inc | Plantas no transgenicas resistentes a los herbicidas. |
| AU2756301A (en) * | 2000-01-03 | 2001-07-16 | Panagenic International, Inc. | Compositions comprising genome segments and methods of using the same |
| US6936467B2 (en) | 2000-03-27 | 2005-08-30 | University Of Delaware | Targeted chromosomal genomic alterations with modified single stranded oligonucleotides |
| MXPA02009627A (es) * | 2000-03-27 | 2004-05-14 | Univ Delaware | Modificaciones genomicas cromosomicas selectivas con oligonucleotidos modificados de un solo filamento.. |
| CA2409172A1 (en) * | 2000-05-17 | 2001-11-22 | University Of Delaware | Plant gene targeting using oligonucleotides |
| US6686188B2 (en) * | 2000-05-26 | 2004-02-03 | Amersham Plc | Polynucleotide encoding a human myosin-like polypeptide expressed predominantly in heart and muscle |
| US6656700B2 (en) | 2000-05-26 | 2003-12-02 | Amersham Plc | Isoforms of human pregnancy-associated protein-E |
| WO2001094610A2 (en) * | 2000-06-05 | 2001-12-13 | Thomas Jefferson University | Binary hybrid mutational vectors |
| AU2001279069A1 (en) * | 2000-07-27 | 2002-02-13 | University Of Delaware | Methods for enhancing targeted gene alteration using oligonucleotides |
| US6875907B2 (en) | 2000-09-13 | 2005-04-05 | Pioneer Hi-Bred International, Inc. | Antimicrobial peptides and methods of use |
| US20020119570A1 (en) * | 2000-09-25 | 2002-08-29 | Kyonggeun Yoon | Targeted gene correction by single-stranded oligodeoxynucleotides |
| US20020123474A1 (en) * | 2000-10-04 | 2002-09-05 | Shannon Mark E. | Human GTP-Rho binding protein2 |
| US7560622B2 (en) | 2000-10-06 | 2009-07-14 | Pioneer Hi-Bred International, Inc. | Methods and compositions relating to the generation of partially transgenic organisms |
| US20040063922A1 (en) * | 2001-04-17 | 2004-04-01 | Conrad Charles A. | Methods and compositions for catalytic DNA exchange in a sequence specific manner |
| US7053195B1 (en) * | 2001-06-12 | 2006-05-30 | Syngenta Participatious Ag | Locked nucleic acid containing heteropolymers and related methods |
| US20040078837A1 (en) * | 2001-08-02 | 2004-04-22 | Shannon Mark E. | Four human zinc-finger-containing proteins: MDZ3, MDZ4, MDZ7 and MDZ12 |
| EP1423537A4 (en) * | 2001-08-07 | 2006-11-29 | Univ Delaware | COMPOSITIONS AND METHODS FOR PREVENTING AND TREATING HUNTINGTON'S DISEASE |
| AU2002322435A1 (en) * | 2001-08-09 | 2003-02-24 | Cibus Genetics | Non-transgenic herbicide resistant plants |
| US20030207327A1 (en) * | 2001-09-27 | 2003-11-06 | Kmiec Eric B. | Coisogenic eukaryotic cell collections |
| WO2003027265A2 (en) * | 2001-09-27 | 2003-04-03 | University Of Delaware | Composition and methods for enhancing oligonucleotide-directed nucleic acid sequence alteration |
| US20030105047A1 (en) * | 2001-11-30 | 2003-06-05 | Medtronic, Inc. | Techniques for treating neurodegenerative disorders by brain infusion of mutational vectors |
| WO2003075856A2 (en) * | 2002-03-07 | 2003-09-18 | University Of Delaware | Methods, compositions, and kits for enhancing oligonucleotide-mediated nucleic acid sequence alteration using compositions comprising a histone deacetylase inhibitor, lambda phage beta protein, or hydroxyurea |
| US20030228558A1 (en) * | 2002-06-11 | 2003-12-11 | Bloom William Dennis | Method of training brokers in a multi-level marketing business |
| JPWO2004026343A1 (ja) * | 2002-09-20 | 2006-01-12 | 住友製薬株式会社 | 部位特異的遺伝子変換促進剤および遺伝子疾患治療剤 |
| US20040175722A1 (en) * | 2002-10-07 | 2004-09-09 | Kmiec Eric B. | Methods and compositions for reducing screening in oligonucleotide-directed nucleic acid sequence alteration |
| EP1570075A2 (en) * | 2002-12-03 | 2005-09-07 | Aarhus Universitet | Method for determing predisposition to manifestation of immune system related diseases |
| US20070072815A1 (en) * | 2004-05-04 | 2007-03-29 | Kmiec Eric B | Methods and kits to increase the efficiency of oligonucleotide-directed nucleic acid sequence alteration |
| CA2592894C (en) | 2004-12-28 | 2013-08-27 | Pioneer Hi-Bred International, Inc. | Improved grain quality through altered expression of gamma-zein protein |
| AU2006216671A1 (en) * | 2005-02-23 | 2006-08-31 | The Uab Research Foundation | Alkyl-glycoside enhanced vaccination |
| WO2006091194A1 (en) | 2005-02-23 | 2006-08-31 | North Carolina State University | Alteration of tobacco alkaloid content through modification of specific cytochrome p450 genes |
| US7680604B2 (en) | 2005-03-11 | 2010-03-16 | Roche Molecular Systems, Inc. | PCR elbow determination by rotational transform after zero slope alignment |
| US20090221670A1 (en) | 2005-05-11 | 2009-09-03 | Aarhus Universitet | Method for diagnosis and treatment of a mental disease |
| NZ564016A (en) | 2005-05-25 | 2009-08-28 | Pioneer Hi Bred Int | Methods for improving crop plant architecture and yield by introducing recombinant expression cassette |
| US7671254B2 (en) * | 2005-08-25 | 2010-03-02 | The Board Of Trustees Of The University Of Illinois | Herbicide resistance gene, compositions and methods |
| US7842856B2 (en) | 2005-08-25 | 2010-11-30 | The Board Of Trustees Of The University Of Illinois | Herbicide resistance gene, compositions and methods |
| CN101356279A (zh) | 2005-11-10 | 2009-01-28 | 先锋高级育种国际公司 | Dof(具有一指的dna结合)序列和使用方法 |
| US20070199096A1 (en) | 2005-11-14 | 2007-08-23 | E.I. Du Pont De Nemours And Company | Compositions and Methods for Altering Alpha- and Beta-Tocotrienol Content |
| WO2007073149A1 (en) * | 2005-12-22 | 2007-06-28 | Keygene N.V. | Alternative nucleotides for improved targeted nucleotide exchange |
| US7592505B2 (en) | 2005-12-30 | 2009-09-22 | Pioneer Hi-Bred International, Inc. | UDP-xylose synthases (UXS) polynucleotides, polypeptides, and uses thereof |
| NZ597682A (en) * | 2006-01-12 | 2014-02-28 | Incima Ipco B V | Epsps mutants |
| RU2313349C2 (ru) | 2006-01-16 | 2007-12-27 | Михаил Аркадьевич Шурдов | Способ лечения онкологических заболеваний |
| CA2640076C (en) | 2006-02-09 | 2013-09-24 | Pioneer Hi-Bred International, Inc. | Genes for enhancing nitrogen utilization efficiency in crop plants |
| EP2007799A2 (en) | 2006-04-19 | 2008-12-31 | Pioneer Hi-Bred International, Inc. | Isolated polynucleotide molecules corresponding to mutant and wild-type alleles of the maize d9 gene and methods of use |
| EP2041047B1 (en) | 2006-06-28 | 2018-10-17 | Cibus Europe B.V. | Fatty acid blends and uses therefor |
| US8710299B2 (en) | 2006-10-06 | 2014-04-29 | Basf Plant Science Gmbh | Processes for producing polyunsaturated fatty acids in transgenic organisms |
| RU2345792C2 (ru) * | 2007-04-03 | 2009-02-10 | Михаил Аркадьевич Шурдов | Способ лечения онкологических заболеваний |
| CN109136210B (zh) | 2007-04-04 | 2022-12-20 | 巴斯福植物科学有限公司 | Ahas突变体 |
| NZ580107A (en) * | 2007-04-04 | 2012-08-31 | Basf Se | Herbicide-resistant brassica plants and methods of use |
| EP2152733A2 (en) | 2007-05-25 | 2010-02-17 | CropDesign N.V. | Yield enhancement in plants by modulation of maize alfins |
| BRPI0818295B1 (pt) * | 2007-10-05 | 2022-10-11 | Cibus Europe B.V. | Método para produção de planta resistente à herbicida |
| EP2220231B1 (en) | 2007-11-12 | 2017-10-11 | North Carolina State University | Alteration of tobacco alkaloid content through modification of specific cytochrome p450 genes |
| US8129586B2 (en) | 2007-11-20 | 2012-03-06 | Pioneer Hi-Bred International, Inc. | Maize ethylene signaling genes and modulation of same for improved stress tolerance in plants |
| RU2515110C2 (ru) | 2007-12-21 | 2014-05-10 | Киджин Н.В. | Улучшенный способ мутагенеза с использованием полиэтиленгликоль-опосредованного введения мутагенных нуклеиновых оснований в растительные протопласты |
| JP2011508047A (ja) * | 2007-12-27 | 2011-03-10 | サイバス,エルエルシー | アルキルエステル脂肪酸配合物およびその用途 |
| EP3260549A1 (en) | 2008-05-23 | 2017-12-27 | Nucelis LLC | Production of squalene using yeast |
| EA201691309A1 (ru) | 2008-09-26 | 2016-11-30 | Басф Агрокемикал Продактс Б.В. | Резистентные к гербицидам ahas-мутанты и способы применения |
| CN102197137A (zh) | 2008-10-30 | 2011-09-21 | 先锋国际良种公司 | 对谷氨酰胺合成酶(gs)进行操作以改善高等植物中的氮利用效率和籽粒产量 |
| CA2743707A1 (en) | 2008-12-04 | 2010-06-10 | Pioneer Hi-Bred International, Inc. | Methods and compositions for enhanced yield by targeted expression of knotted1 |
| EP2669380B1 (en) | 2008-12-12 | 2017-09-27 | BASF Plant Science GmbH | Desaturases and process for the production of polyunsaturated fatty acids in transgenic organisms |
| JP2012513199A (ja) | 2008-12-22 | 2012-06-14 | キージーン・エン・フェー | 植物プロトプラストにおける標的化遺伝子改変の効率を増大させるための二本鎖rnaの使用 |
| AU2010204723A1 (en) | 2009-01-14 | 2011-08-18 | The Salk Institute For Biological Studies | Methods for screening and compounds that protect against amyloid diseases |
| US8716553B2 (en) | 2009-03-02 | 2014-05-06 | Pioneer Hi Bred International Inc | NAC transcriptional activators involved in abiotic stress tolerance |
| UA108071C2 (uk) | 2009-04-14 | 2015-03-25 | Піонер Хай-Бред Інтернешнл, Інк. | Спосіб поліпшення витривалості до нестачі азоту у рослини |
| WO2010129501A1 (en) | 2009-05-04 | 2010-11-11 | Pioneer Hi-Bred International, Inc. | Yield enhancement in plants by modulation of ap2 transcription factor |
| EA201200177A1 (ru) | 2009-07-24 | 2012-06-29 | Пайонир Хай-Бред Интернэшнл, Инк. | Применение связок компонентов домена димеризации для регулирования архитектуры растения |
| RU2429019C2 (ru) * | 2009-08-03 | 2011-09-20 | Михаил Аркадьевич Шурдов | Способ лечения онкологических заболеваний |
| WO2011017492A2 (en) | 2009-08-05 | 2011-02-10 | Pioneer Hi-Bred International, Inc. | Novel eto1 genes and use of same for reduced ethylene and improved stress tolerance in plants |
| IN2012DN02408A (OSRAM) | 2009-10-02 | 2015-08-21 | Pioneer Hi Bred Int | |
| CN107058145A (zh) | 2009-11-23 | 2017-08-18 | 纽塞利斯公司 | 使用酵母产生角鲨烯的方法和组合物 |
| CA2786001A1 (en) | 2009-12-31 | 2011-07-07 | Pioneer Hi-Bred International, Inc. | Engineering plant resistance to diseases caused by pathogens |
| CN102906267A (zh) | 2010-01-06 | 2013-01-30 | 先锋国际良种公司 | 玉米光合作用组织和非光合作用组织昼夜节律的鉴定及其在改良作物方面的用途 |
| CA2818599A1 (en) | 2010-01-26 | 2011-08-04 | Bailin Li | Polynucleotide and polypeptide sequences associated with herbicide tolerance |
| WO2011139431A1 (en) | 2010-05-06 | 2011-11-10 | Pioneer Hi-Bred International, Inc. | Maize acc synthase 3 gene and protein and uses thereof |
| US20120122223A1 (en) | 2010-08-03 | 2012-05-17 | Cibus Us Llc | Mutated protoporphyrinogen ix oxidase (ppx) genes |
| UA112969C2 (uk) | 2010-08-03 | 2016-11-25 | Сібас Юс Ллс | Рослина, стійка до одного або більше ррх-інгібуючих гербіцидів, яка містить мутантний ген протопорфіриноген ix оксидази (ррх) |
| BR112013003224A2 (pt) | 2010-08-13 | 2016-06-07 | Pioneer Hi Bred Int | "construto de promotor quimérico, cassete de expressão, vetor de expressão, método de obtenção de uma planta, método para regular a expressão de um polinucleotídeo de interesse, polinucleotídeo, método para expressar um polinucleotídeo de interesse" |
| EP2426204A1 (en) | 2010-09-02 | 2012-03-07 | Ludwig-Maximilians-Universität München | Spontaneous nodule organogenesis in plants |
| WO2012028673A1 (en) | 2010-09-02 | 2012-03-08 | Ludwig-Maximilians-Universitaet Muenchen | Spontaneous organogenesis in plants |
| ES2588482T3 (es) | 2010-12-02 | 2016-11-03 | Keygene N.V. | Alteración dirigida de ADN |
| AU2011337324B2 (en) | 2010-12-02 | 2015-11-26 | Keygene N.V. | Targeted alteration of DNA with oligonucleotides |
| US9677084B2 (en) | 2011-04-29 | 2017-06-13 | Pioneer Hi-Bred International, Inc. | Down-regulation of a homeodomain-leucine zipper I-class homeobox gene for improved plant performance |
| WO2012174139A2 (en) | 2011-06-14 | 2012-12-20 | Synthon Biopharmaceuticals B.V. | Compositions and methods for making and b ioc ont aining auxotrophic transgenic plants |
| WO2013009935A2 (en) | 2011-07-12 | 2013-01-17 | Two Blades Foundation | Late blight resistance genes |
| CA2853775A1 (en) | 2011-10-31 | 2013-05-10 | Pioneer Hi-Bred International, Inc. | Improving plant drought tolerance, nitrogen use efficiency and yield |
| EA201491670A1 (ru) | 2012-03-13 | 2015-07-30 | Пайонир Хай-Бред Интернэшнл, Инк. | Генетическое снижение мужской репродуктивной функции у растений |
| WO2013138309A1 (en) | 2012-03-13 | 2013-09-19 | Pioneer Hi-Bred International, Inc. | Genetic reduction of male fertility in plants |
| US10045499B2 (en) | 2012-05-24 | 2018-08-14 | Iowa State University Research Foundation, Inc. | Arabidopsis nonhost resistance gene(s) and use thereof to engineer disease resistant plants |
| US10006041B2 (en) | 2012-08-16 | 2018-06-26 | Vib Vzw | Means and methods for altering the lignin pathway in plants |
| US20150351390A1 (en) | 2012-12-21 | 2015-12-10 | Pioneer Hi-Bred International, Inc. | Compositions and methods for auxin-analog conjugation |
| WO2014164014A1 (en) | 2013-03-11 | 2014-10-09 | Pioneer Hi-Bred International, Inc. | Genes for improving nutrient uptake and abiotic stress tolerance in plants |
| US9803214B2 (en) | 2013-03-12 | 2017-10-31 | Pioneer Hi-Bred International, Inc. | Breeding pair of wheat plants comprising an MS45 promoter inverted repeat that confers male sterility and a construct that restores fertility |
| WO2014164466A1 (en) | 2013-03-12 | 2014-10-09 | E. I. Du Pont De Nemours And Company | Methods for the identification of variant recognition sites for rare-cutting engineered double-strand-break-inducing agents and compositions and uses thereof |
| WO2014164074A1 (en) | 2013-03-13 | 2014-10-09 | Pioneer Hi-Bred International, Inc. | Enhanced nitrate uptake and nitrate translocation by over-expressing maize functional low-affinity nitrate transporters in transgenic maize |
| US20160017360A1 (en) | 2013-03-13 | 2016-01-21 | Pioneer Hi-Bred International, Inc. | Functional expression of bacterial major facilitator superfamily mfs gene in maize to improve agronomic traits and grain yield |
| WO2014160122A1 (en) | 2013-03-14 | 2014-10-02 | Pioneer Hi-Bred International, Inc. | Maize stress related transcription factor 18 and uses thereof |
| UA119745C2 (uk) | 2013-03-14 | 2019-08-12 | Сібас Юс Ллс | Мутований ген аленоксидсинтази 2 (aos2) |
| WO2014152507A2 (en) | 2013-03-15 | 2014-09-25 | Pioneer Hi-Bred International, Inc. | Modulation of acc deaminase expression |
| WO2014144987A2 (en) | 2013-03-15 | 2014-09-18 | Cibus Us Llc | Methods and compositions for increasing efficiency of increased efficiency of targeted gene modification using oligonucleotide-mediated gene repair |
| US9957515B2 (en) | 2013-03-15 | 2018-05-01 | Cibus Us Llc | Methods and compositions for targeted gene modification |
| CN105143454A (zh) | 2013-03-15 | 2015-12-09 | 先锋国际良种公司 | Acc氧化酶多核苷酸和多肽的组合物和使用方法 |
| CN108823238B (zh) | 2013-03-15 | 2022-02-01 | 希博斯美国有限公司 | 采用寡核苷酸介导的基因修复提高靶向基因修饰的效率的方法和组合物 |
| US12331303B2 (en) | 2013-03-15 | 2025-06-17 | Cibus Us Llc | Methods and compositions for increasing efficiency of targeted gene modification using oligonucleotide-mediated gene repair |
| AU2014234265B2 (en) | 2013-03-21 | 2020-01-30 | Universiteit Gent | Means and methods for the reduction of photorespiration in crops |
| WO2015006105A1 (en) | 2013-07-09 | 2015-01-15 | Board Of Trustees Of Michigan State University | Transgenic plants produced with a k-domain, and methods and expression cassettes related thereto |
| US11459579B2 (en) | 2013-07-09 | 2022-10-04 | Board Of Trustees Of Michigan State University | Transgenic plants produced with a K-domain, and methods and expression cassettes related thereto |
| US20170166920A1 (en) | 2014-01-30 | 2017-06-15 | Two Blades Foundation | Plants with enhanced resistance to phytophthora |
| SI3116305T1 (sl) | 2014-03-14 | 2024-05-31 | Cibus Us Llc | Metode in sestavki za povečanje učinkovitosti ciljne genske modifikacije z uporabo popravila gena, posredovanega z oligonukleotidi |
| WO2015171603A1 (en) | 2014-05-06 | 2015-11-12 | Two Blades Foundation | Methods for producing plants with enhanced resistance to oomycete pathogens |
| US20170159065A1 (en) | 2014-07-08 | 2017-06-08 | Vib Vzw | Means and methods to increase plant yield |
| WO2016057515A2 (en) | 2014-10-06 | 2016-04-14 | Altria Client Services Llc | Genetic control of axillary bud growth in tobacco plants |
| WO2016100309A1 (en) | 2014-12-16 | 2016-06-23 | Pioneer Hi-Bred International, Inc. | Restoration of male fertility in wheat |
| WO2016105185A1 (en) | 2014-12-22 | 2016-06-30 | Keygene N.V. | Plant callus populations |
| US11697820B2 (en) | 2015-05-09 | 2023-07-11 | Two Blades Foundation | Late blight resistance gene from Solanum americanum and methods of use |
| WO2017062790A1 (en) | 2015-10-09 | 2017-04-13 | Two Blades Foundation | Cold shock protein receptors and methods of use |
| US11542515B2 (en) | 2016-02-09 | 2023-01-03 | Cibus Us Llc | Methods and compositions for increasing efficiency of targeted gene modification using oligonucleotide-mediated gene repair |
| CN117089526A (zh) | 2016-03-11 | 2023-11-21 | 奥驰亚客户服务有限公司 | 用于生产烟杈减少或消除的烟草植物和制品的组合物和方法 |
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| WO2018067985A1 (en) | 2016-10-07 | 2018-04-12 | Altria Client Services Llc | Composition and methods for producing tobacco plants and products having reduced tobacco-specific nitrosamines (tsnas) |
| US11643432B2 (en) | 2016-12-16 | 2023-05-09 | National University Corporation Tokai National Higher Education And Research System | Nucleoside derivative and use thereof |
| CN110462047B (zh) | 2016-12-16 | 2024-12-27 | 双刃基金会 | 晚疫病抗性基因及使用方法 |
| WO2018140214A1 (en) | 2017-01-24 | 2018-08-02 | Pioneer Hi-Bred International, Inc. | Nematicidal protein from pseudomonas |
| CN111542608A (zh) | 2017-07-28 | 2020-08-14 | 双刃基金会 | 马铃薯y病毒抗性基因及使用方法 |
| JP2020533000A (ja) | 2017-09-11 | 2020-11-19 | アルトリア クライアント サーヴィシーズ リミテッド ライアビリティ カンパニー | 吸枝が減少又は消失したタバコ植物及びタバコ製品を生産する組成物及び方法 |
| WO2019088179A1 (ja) | 2017-10-31 | 2019-05-09 | ヤマサ醤油株式会社 | ヌクレオシド誘導体及びその利用 |
| WO2019108619A1 (en) | 2017-11-28 | 2019-06-06 | Two Blades Foundation | Methods and compositions for enhancing the disease resistance of plants |
| US11034969B2 (en) | 2017-12-22 | 2021-06-15 | Altria Client Services Llc | Plant comprising recombinant polynucleotides encoding a pigment regulatory transcription factor with a tissue-preferred promoter |
| CN118830491A (zh) | 2018-01-09 | 2024-10-25 | 希博斯美国有限公司 | 防碎基因和突变 |
| WO2019140351A1 (en) | 2018-01-12 | 2019-07-18 | Two Blades Foundation | Stem rust resistance genes and methods of use |
| EP3773017B1 (en) | 2018-04-03 | 2022-06-08 | Altria Client Services LLC | Composition and methods for producing tobacco plants and products having increased phenylalanine and reduced tobacco-specific nitrosamines (tsnas) |
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| US12077765B2 (en) | 2019-01-24 | 2024-09-03 | Altria Client Services Llc | Tobacco plants comprising reduced nicotine and reduced tobacco specific nitrosamines |
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| AU2022324708A1 (en) | 2021-08-06 | 2024-02-15 | Kws Vegetables B.V. | Durable downy mildew resistance in spinach |
| CA3233676A1 (en) | 2021-09-30 | 2023-04-06 | The Sainsbury Laboratory | Plant disease resistance genes against stem rust and methods of use |
| WO2023131616A1 (en) | 2022-01-05 | 2023-07-13 | Vib Vzw | Means and methods to increase abiotic stress tolerance in plants |
| WO2023131637A1 (en) | 2022-01-06 | 2023-07-13 | Vib Vzw | Improved silage grasses |
| WO2023144199A1 (en) | 2022-01-26 | 2023-08-03 | Vib Vzw | Plants having reduced levels of bitter taste metabolites |
| AR133243A1 (es) | 2023-07-14 | 2025-09-10 | Two Blades Found | Métodos para mejorar la termoestabilidad de los receptores inmunitarios de plantas |
| WO2025019221A1 (en) | 2023-07-15 | 2025-01-23 | Two Blades Foundation | Broad-spectrum polerovirus resistance gene |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4503151A (en) * | 1980-12-10 | 1985-03-05 | Research Corporation | Recombinant cDNA construction method and hybrid nucleotides useful in cloning |
| US4882279A (en) * | 1985-10-25 | 1989-11-21 | Phillips Petroleum Company | Site selective genomic modification of yeast of the genus pichia |
| EP0260032B1 (en) * | 1986-09-08 | 1994-01-26 | Ajinomoto Co., Inc. | Compounds for the cleavage at a specific position of RNA, oligomers employed for the formation of said compounds, and starting materials for the synthesis of said oligomers |
| ATE190981T1 (de) * | 1989-10-24 | 2000-04-15 | Isis Pharmaceuticals Inc | 2'-modifizierte nukleotide |
| EP0626012B1 (en) * | 1992-02-11 | 2003-07-09 | Cell Genesys, Inc. | Homogenotization of gene-targeting events |
| CA2178729A1 (en) * | 1993-12-09 | 1995-06-15 | Eric B. Kmiec | Compounds and methods for site-directed mutations in eukaryotic cells |
| US5760012A (en) * | 1996-05-01 | 1998-06-02 | Thomas Jefferson University | Methods and compounds for curing diseases caused by mutations |
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