AU708658B2 - Methods and compounds for curing diseases caused by mutations - Google Patents
Methods and compounds for curing diseases caused by mutations Download PDFInfo
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- AU708658B2 AU708658B2 AU28225/97A AU2822597A AU708658B2 AU 708658 B2 AU708658 B2 AU 708658B2 AU 28225/97 A AU28225/97 A AU 28225/97A AU 2822597 A AU2822597 A AU 2822597A AU 708658 B2 AU708658 B2 AU 708658B2
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- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- 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
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
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- A61P7/06—Antianaemics
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- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- 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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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- C07K14/795—Porphyrin- or corrin-ring-containing peptides
- C07K14/805—Haemoglobins; Myoglobins
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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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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- C12N2310/00—Structure or type of the nucleic acid
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- C12N2310/321—2'-O-R Modification
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| US08/640,517 US5760012A (en) | 1996-05-01 | 1996-05-01 | Methods and compounds for curing diseases caused by mutations |
| US08/640517 | 1996-05-01 | ||
| PCT/US1997/007362 WO1997041141A1 (en) | 1996-05-01 | 1997-05-01 | Methods and compounds for curing diseases caused by mutations |
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| AU2822597A AU2822597A (en) | 1997-11-19 |
| AU708658B2 true AU708658B2 (en) | 1999-08-12 |
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| US (1) | US5760012A (show.php) |
| EP (1) | EP0906328A4 (show.php) |
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| NZ (1) | NZ332297A (show.php) |
| WO (1) | WO1997041141A1 (show.php) |
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| US5888983A (en) * | 1996-05-01 | 1999-03-30 | Thomas Jefferson University | Method and oligonucleobase compounds for curing diseases caused by mutations |
| US5731181A (en) * | 1996-06-17 | 1998-03-24 | Thomas Jefferson University | Chimeric mutational vectors having non-natural nucleotides |
| US20040266706A1 (en) * | 2002-11-05 | 2004-12-30 | Muthiah Manoharan | Cross-linked oligomeric compounds and their use in gene modulation |
| US6524613B1 (en) | 1997-04-30 | 2003-02-25 | Regents Of The University Of Minnesota | Hepatocellular chimeraplasty |
| US7094606B2 (en) | 1997-08-05 | 2006-08-22 | Arntzen Charles J | Use of mixed duplex oligonucleotides to effect localized genetic changes in plants |
| US6004804A (en) * | 1998-05-12 | 1999-12-21 | Kimeragen, Inc. | Non-chimeric mutational vectors |
| US6010907A (en) * | 1998-05-12 | 2000-01-04 | Kimeragen, Inc. | Eukaryotic use of non-chimeric mutational vectors |
| US6438561B1 (en) * | 1998-11-19 | 2002-08-20 | Navigation Technologies Corp. | Method and system for using real-time traffic broadcasts with navigation systems |
| US6917882B2 (en) * | 1999-01-19 | 2005-07-12 | Maxygen, Inc. | Methods for making character strings, polynucleotides and polypeptides having desired characteristics |
| US20030054390A1 (en) * | 1999-01-19 | 2003-03-20 | Maxygen, Inc. | Oligonucleotide mediated nucleic acid recombination |
| US6376246B1 (en) | 1999-02-05 | 2002-04-23 | Maxygen, Inc. | Oligonucleotide mediated nucleic acid recombination |
| US6368861B1 (en) | 1999-01-19 | 2002-04-09 | Maxygen, Inc. | Oligonucleotide mediated nucleic acid recombination |
| US6961664B2 (en) | 1999-01-19 | 2005-11-01 | Maxygen | Methods of populating data structures for use in evolutionary simulations |
| US7024312B1 (en) * | 1999-01-19 | 2006-04-04 | Maxygen, Inc. | Methods for making character strings, polynucleotides and polypeptides having desired characteristics |
| US20070065838A1 (en) * | 1999-01-19 | 2007-03-22 | Maxygen, Inc. | Oligonucleotide mediated nucleic acid recombination |
| ATE465459T1 (de) | 1999-01-19 | 2010-05-15 | Maxygen Inc | Durch oligonukleotide-vermittelte nukleinsäuren- rekombination |
| AU4188100A (en) * | 1999-04-08 | 2000-11-14 | Gregory M. Glenn | Dry formulation for transcutaneous immunization |
| WO2000071165A2 (en) * | 1999-05-21 | 2000-11-30 | The University Of Miami | Use of chimeric mutational vectors to change endogenous sequences in solid tissues |
| US6830902B1 (en) * | 1999-07-02 | 2004-12-14 | Invitrogen Corporation | Compositions and methods for enhanced sensitivity and specificity of nucleic acid synthesis |
| WO2001002559A1 (en) * | 1999-07-02 | 2001-01-11 | Invitrogen Corporation | Compositions and methods for enhanced sensitivity and specificity of nucleic acid synthesis |
| US6271360B1 (en) | 1999-08-27 | 2001-08-07 | Valigen (Us), Inc. | Single-stranded oligodeoxynucleotide mutational vectors |
| AR025996A1 (es) | 1999-10-07 | 2002-12-26 | Valigen Us Inc | Plantas no transgenicas resistentes a los herbicidas. |
| US7430477B2 (en) * | 1999-10-12 | 2008-09-30 | Maxygen, Inc. | Methods of populating data structures for use in evolutionary simulations |
| US6656700B2 (en) | 2000-05-26 | 2003-12-02 | Amersham Plc | Isoforms of human pregnancy-associated protein-E |
| US6686188B2 (en) * | 2000-05-26 | 2004-02-03 | Amersham Plc | Polynucleotide encoding a human myosin-like polypeptide expressed predominantly in heart and muscle |
| WO2001094610A2 (en) * | 2000-06-05 | 2001-12-13 | Thomas Jefferson University | Binary hybrid mutational vectors |
| US6875907B2 (en) | 2000-09-13 | 2005-04-05 | Pioneer Hi-Bred International, Inc. | Antimicrobial peptides and methods of use |
| US20020123474A1 (en) * | 2000-10-04 | 2002-09-05 | Shannon Mark E. | Human GTP-Rho binding protein2 |
| WO2002079495A2 (en) * | 2001-03-27 | 2002-10-10 | University Of Delaware | Genomics applications for modified oligonucleotides |
| US20030045830A1 (en) * | 2001-04-17 | 2003-03-06 | De Bizemont Therese | Gene therapy with chimeric oligonucleotides delivered by a method comprising a step of iontophoresis |
| US20040063922A1 (en) * | 2001-04-17 | 2004-04-01 | Conrad Charles A. | Methods and compositions for catalytic DNA exchange in a sequence specific manner |
| US20040078837A1 (en) * | 2001-08-02 | 2004-04-22 | Shannon Mark E. | Four human zinc-finger-containing proteins: MDZ3, MDZ4, MDZ7 and MDZ12 |
| AU2002322435A1 (en) * | 2001-08-09 | 2003-02-24 | Cibus Genetics | Non-transgenic herbicide resistant plants |
| WO2003027264A2 (en) * | 2001-09-27 | 2003-04-03 | University Of Delaware | Coisogenic eukaryotic cell collections |
| US7468244B2 (en) * | 2001-09-27 | 2008-12-23 | University Of Delaware | Polymorphism detection and separation |
| ATE458047T1 (de) * | 2002-03-07 | 2010-03-15 | Univ Delaware | Verfahren zur verstärkung der oligonucleotid- vermittelten nucleinsäuresequenzänderung unter verwendung von zusammensetzungen mit einem hydroxyharnstoff |
| IL166546A0 (en) | 2002-08-05 | 2006-01-15 | Atugen Ag | Further novel forms of interfering ran molecules |
| WO2004033708A2 (en) * | 2002-10-07 | 2004-04-22 | University Of Delaware | Methods and compositions for reducing screening in oligonucleotide-directed nucleic acid sequence alteration |
| AU2003283217A1 (en) * | 2002-12-03 | 2004-06-23 | Aarhus Amt | Method for determing predisposition to manifestation of immune system related diseases |
| US20050025753A1 (en) * | 2003-04-30 | 2005-02-03 | Wei Han | Methods for production of non-disease causing hemoglobin by ex vivo oligonucleotide gene editing of human stem/progenitor cells |
| 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 |
| AU2004326206B2 (en) | 2004-12-28 | 2011-03-17 | Pioneer Hi-Bred International, Inc. | Improved grain quality through altered expression of seed proteins |
| BRPI0519985B1 (pt) | 2005-02-23 | 2018-01-30 | University Of Kentucky Research Foundation | Método para redução do nível de nornicotina ou n-nitrosonornicotina em uma planta do gênero nicotiana ou parte desta ou em um produto de tabaco, cassete de expressão e método para a produção de uma planta do gênero nicotiana |
| US20090221670A1 (en) | 2005-05-11 | 2009-09-03 | Aarhus Universitet | Method for diagnosis and treatment of a mental disease |
| EP2261361A3 (en) | 2005-05-25 | 2011-04-20 | Pioneer Hi-Bred International Inc. | Methods for improving crop plant architecture and yield |
| CN1880458B (zh) * | 2005-06-15 | 2010-04-28 | 中国医学科学院基础医学研究所 | 人β-珠蛋白基因簇的人源染色体打靶载体及其应用 |
| CA2629521A1 (en) | 2005-11-10 | 2007-05-24 | Pioneer Hi-Bred International, Inc. | Dof (dna binding with one finger) sequences and methods of use |
| 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 |
| US7592505B2 (en) | 2005-12-30 | 2009-09-22 | Pioneer Hi-Bred International, Inc. | UDP-xylose synthases (UXS) polynucleotides, polypeptides, and uses thereof |
| EP2923563B1 (en) | 2006-01-12 | 2024-09-18 | Cibus Europe B.V. | EPSPS mutants |
| AU2007212168A1 (en) | 2006-02-09 | 2007-08-16 | Pioneer Hi-Bred International, Inc. | Genes for enhancing nitrogen utilization efficiency in crop plants |
| MX2008013354A (es) | 2006-04-19 | 2008-11-10 | Pioneer Hi Bred Int | Moleculas de polinucleotidos aislados que corresponden a alelos mutantes y tipo salvaje del gen de maiz d9, y metodos para usarlas. |
| UA107442C2 (uk) * | 2006-06-28 | 2015-01-12 | Nucelis Inc | Суміш жирних кислот та її застосування |
| AU2007363151B2 (en) * | 2006-06-28 | 2014-12-11 | Cibus Europe B.V. | Alkylester fatty acid blends and uses therefor |
| EP2574233A1 (en) | 2007-04-04 | 2013-04-03 | BASF Plant Science GmbH | AHAS mutants |
| BRPI0811242A2 (pt) | 2007-05-25 | 2014-11-04 | Cropdesign Nv | Polinucleotídeo isolado, cassete de expressão, planta, métodos para aumentar o nível de um polipeptídeo em uma planta, e para aumentar o rendimento em uma planta, e, polipeptídeo isolado |
| US20090205064A1 (en) * | 2007-10-05 | 2009-08-13 | Christian Schopke | Mutated Acetohydroxyacid Synthase Genes in Brassica |
| CN101939431B (zh) | 2007-11-12 | 2015-01-28 | 北卡罗来纳州立大学 | 通过修饰特定细胞色素p450基因改变烟草生物碱含量 |
| AR069392A1 (es) | 2007-11-20 | 2010-01-20 | Pioneer Hi Bred Int | Genes de senalizacion de etileno en maiz y su modulacion para aumentar la tolerancia al estres en plantas |
| EP2279255A4 (en) * | 2008-05-23 | 2012-03-07 | Coh Inc | PREPARATION OF SQUALES BY YEAST |
| CN102216453B (zh) | 2008-09-26 | 2014-02-05 | 巴斯夫农化产品有限公司 | 除草剂-抗性的ahas-突变体及使用方法 |
| EP2344640A1 (en) | 2008-10-30 | 2011-07-20 | Pioneer Hi-Bred International Inc. | Manipulation of glutamine synthetases (gs) to improve nitrogen use efficiency and grain yield in higher plants |
| US8431775B2 (en) | 2008-12-04 | 2013-04-30 | Pioneer Hi Bred International Inc | Methods and compositions for enhanced yield by targeted expression of knotted1 |
| JP2012515214A (ja) | 2009-01-14 | 2012-07-05 | トヘ サルク インストイトウテ フオル ビオルオギクアル ストウドイエス | スクリーニング方法、及びアミロイド病に対し保護する化合物 |
| WO2010101818A1 (en) | 2009-03-02 | 2010-09-10 | Pioneer Hi-Bred International, Inc. | Nac transcriptional activators involved in abiotic stress tolerance |
| CA2757581A1 (en) | 2009-04-14 | 2010-10-21 | Pioneer Hi-Bred International, Inc. | Modulation of acc synthase improves plant yield under low nitrogen conditions |
| MX2011011678A (es) | 2009-05-04 | 2011-12-06 | Pioneer Hi Bred Int | Mejora de la produccion en plantas mediante la modulacion del factor de transcripcion ap2. |
| EA201200177A1 (ru) | 2009-07-24 | 2012-06-29 | Пайонир Хай-Бред Интернэшнл, Инк. | Применение связок компонентов домена димеризации для регулирования архитектуры растения |
| 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 |
| CA2775093A1 (en) | 2009-10-02 | 2011-04-07 | Pioneer Hi-Bred International, Inc. | Down-regulation of acc synthase for improved plant performance |
| CA2781303A1 (en) * | 2009-11-23 | 2011-05-26 | Nucelis Inc. | Methods and compositions for producing squalene using yeast |
| WO2011082304A1 (en) | 2009-12-31 | 2011-07-07 | Pioneer Hi-Bred International, Inc. | Engineering plant resistance to diseases caused by pathogens |
| MX2012007855A (es) | 2010-01-06 | 2013-06-05 | Du Pont | Identificacion de ritmos diurnos en tejidos fotosinteticos del zea mays y uso en el mejoramiento de plantas de cultivo. |
| EP2529027A1 (en) | 2010-01-26 | 2012-12-05 | Pioneer-Hi-Bred International, Inc. | Hppd-inhibitor herbicide tolerance |
| EP2566962A1 (en) | 2010-05-06 | 2013-03-13 | 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) |
| WO2012021794A1 (en) | 2010-08-13 | 2012-02-16 | Pioneer Hi-Bred International, Inc. | Chimeric promoters and methods of use |
| WO2012028673A1 (en) | 2010-09-02 | 2012-03-08 | Ludwig-Maximilians-Universitaet Muenchen | Spontaneous organogenesis in plants |
| EP2426204A1 (en) | 2010-09-02 | 2012-03-07 | Ludwig-Maximilians-Universität München | Spontaneous nodule organogenesis in plants |
| CN103502269A (zh) | 2011-04-29 | 2014-01-08 | 先锋国际良种公司 | 下调同源域-亮氨酸拉链i类同源盒基因以改进植物性能 |
| EP2721160A2 (en) | 2011-06-14 | 2014-04-23 | Synthon Biopharmaceuticals B.V. | Compositions and methods for making and biocontaining auxotrophic transgenic plants |
| US20130097734A1 (en) | 2011-07-12 | 2013-04-18 | Two Blades Foundation | Late blight resistance genes |
| BR112014010537A2 (pt) | 2011-10-31 | 2017-05-02 | Pioneer Hi Bred Int | método para modular a sensibilidade ao etileno, planta transgênica, proteína isolada, sequência de polinucleotídeos isolada, polipeptídeo com atividade regulatória de etileno, método para aumentar o rendimento em uma planta, método para melhorar um parâmetro agronômico de uma planta, método de seleção assistida por marcador de uma planta |
| MX2014011038A (es) | 2012-03-13 | 2015-06-02 | Pioneer Hi Bred Int | Reduccion genetica de la fertilidad masculina en plantas. |
| 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 |
| WO2014011901A2 (en) * | 2012-07-11 | 2014-01-16 | Sangamo Biosciences, Inc. | Methods and compositions for delivery of biologics |
| EP2885411B1 (en) | 2012-08-16 | 2018-12-05 | VIB vzw | Means and methods for altering the lignin pathway in plants |
| CN105008541A (zh) | 2012-12-21 | 2015-10-28 | 先锋国际良种公司 | 用于生长素类似物缀合的组合物和方法 |
| 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 |
| US20160010101A1 (en) | 2013-03-13 | 2016-01-14 | Pioneer Hi-Bred International, Inc. | Enhanced nitrate uptake and nitrate translocation by over- expressing maize functional low-affinity nitrate transporters in transgenic maize |
| WO2014164116A1 (en) | 2013-03-13 | 2014-10-09 | Pioneer Hi-Bred International, Inc. | Functional expression of bacterial major facilitator superfamily (sfm) gene in maize to improve agronomic traits and grain yield |
| UA119745C2 (uk) | 2013-03-14 | 2019-08-12 | Сібас Юс Ллс | Мутований ген аленоксидсинтази 2 (aos2) |
| US20160024513A1 (en) | 2013-03-14 | 2016-01-28 | Pioneer Hi-Bred International Inc. | Maize stress related transcription factor 18 and uses thereof |
| US9957515B2 (en) | 2013-03-15 | 2018-05-01 | Cibus Us Llc | Methods and compositions for targeted gene modification |
| LT3527068T (lt) | 2013-03-15 | 2022-08-10 | Cibus Us Llc | Būdai ir kompozicijos, skirti padidinti tikslinės geno modifikacijos efektyvumą, panaudojant geno reparaciją, kuriai tarpininkauja oligonukleotidas |
| ES2912400T3 (es) | 2013-03-15 | 2022-05-25 | Cibus Us Llc | Modificación génica orientada mediante la reparación génica mediada por oligonucleótidos |
| BR112015023703A2 (pt) | 2013-03-15 | 2017-07-18 | Pioneer Hi Bred Int | modulação de expressão de deaminase de acc |
| 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 |
| CA2903555A1 (en) | 2013-03-15 | 2014-09-18 | Pioneer Hi-Bred International, Inc. | Compositions and methods of use of acc oxidase polynucleotides and polypeptides |
| CA2904817C (en) | 2013-03-21 | 2022-10-18 | Vib Vzw | Means and methods for the reduction of photorespiration in crops |
| 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 |
| US10570409B2 (en) | 2013-07-09 | 2020-02-25 | 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 |
| FI3116305T3 (fi) | 2014-03-14 | 2024-02-08 | Cibus Us Llc | Menetelmät ja koostumukset kohdennetun geenimuunnoksen tehokkuuden lisäämiseksi käyttämällä oligonukleotidivälitteistä geeninkorjausta |
| WO2015171603A1 (en) | 2014-05-06 | 2015-11-12 | Two Blades Foundation | Methods for producing plants with enhanced resistance to oomycete pathogens |
| WO2016005449A1 (en) | 2014-07-08 | 2016-01-14 | Vib Vzw | Means and methods to increase plant yield |
| EP3470521B1 (en) | 2014-10-06 | 2020-07-15 | Altria Client Services LLC | Genetic control of axillary bud growth in tobacco plants |
| US20170369902A1 (en) | 2014-12-16 | 2017-12-28 | Pioneer Hi-Bred International, Inc. | Restoration of male fertility in wheat |
| 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 |
| WO2017138986A1 (en) | 2016-02-09 | 2017-08-17 | 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 |
| JP7066126B2 (ja) | 2016-08-09 | 2022-05-13 | ブイアイビー ブイゼットダブリュ | セルロースシンターゼ阻害剤および突然変異体植物 |
| EP3523439A1 (en) | 2016-10-07 | 2019-08-14 | Altria Client Services LLC | Composition and methods for producing tobacco plants and products having reduced tobacco-specific nitrosamines (tsnas) |
| 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 |
| EP3658675A1 (en) | 2017-07-28 | 2020-06-03 | Two Blades Foundation | Potyvirus resistance genes and methods of use |
| WO2019051232A1 (en) | 2017-09-11 | 2019-03-14 | Altria Client Services Llc | COMPOSITIONS AND METHODS FOR PRODUCING TOBACCO PLANTS AND PRODUCTS HAVING REDUCED OR ELIMINATED GOURMETS |
| WO2019108619A1 (en) | 2017-11-28 | 2019-06-06 | Two Blades Foundation | Methods and compositions for enhancing the disease resistance of plants |
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| WO2019140009A1 (en) | 2018-01-09 | 2019-07-18 | Cibus Us Llc | Shatterproof genes and mutations |
| CN111954464A (zh) | 2018-01-12 | 2020-11-17 | 双刃基金会 | 秆锈病抗性基因及使用方法 |
| WO2019195237A1 (en) | 2018-04-03 | 2019-10-10 | Altria Client Services Llc | Composition and methods for producing tobacco plants and products having increased phenylalanine and reduced tobacco-specific nitrosamines (tsnas) |
| UA129286C2 (uk) | 2018-04-04 | 2025-03-12 | Сайбас Юес Ллс | Гени fad2 і мутації |
| GB201815670D0 (en) * | 2018-09-26 | 2018-11-07 | Univ Oxford Innovation Ltd | Protein editing |
| US12077765B2 (en) | 2019-01-24 | 2024-09-03 | Altria Client Services Llc | Tobacco plants comprising reduced nicotine and reduced tobacco specific nitrosamines |
| CN112111528B (zh) * | 2019-06-21 | 2024-04-02 | 华东师范大学 | 一种内含子异常剪接的修复方法 |
| AR122276A1 (es) | 2019-06-27 | 2022-08-31 | Two Blades Found | Receptores de reconocimiento del patrón atrlp23 manipulados por ingeniería y métodos de uso |
| WO2021011348A1 (en) | 2019-07-12 | 2021-01-21 | The Regents Of The University Of California | Plants with enhanced resistance to bacterial pathogens |
| BR112023023667A2 (pt) | 2021-05-11 | 2024-01-30 | Two Blades Found | Métodos para preparar uma biblioteca de genes de resistência à doença de planta e à praga de planta, para identificar um gene de resistência à doença de planta e à praga de planta, para produzir uma planta com resistência aprimorada a uma doença de planta e para limitar uma doença de planta na produção de safras agrícolas, biblioteca de genes de resistência candidatos, planta transgênica, coleção de plantas transgênicas, planta ou célula de planta resistente compreendendo um gene de resistência, gene de resistência isolado, célula hospedeira, molécula de ácido nucleico, cassete de expressão, vetor, planta de trigo, semente de trigo ou célula de trigo, planta ou semente transgênica, planta, semente da planta, uso da planta ou semente, produto alimentício humano ou animal, e, polipeptídeo |
| EP4380352A1 (en) | 2021-08-06 | 2024-06-12 | KWS Vegetables B.V. | Durable downy mildew resistance in spinach |
| US20250002929A1 (en) | 2021-09-30 | 2025-01-02 | The Sainsbury Laboratory | Plant disease resistance genes against stem rust and methods of use |
| EP4460571A1 (en) | 2022-01-05 | 2024-11-13 | 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 |
| WO2025019221A1 (en) | 2023-07-15 | 2025-01-23 | Two Blades Foundation | Broad-spectrum polerovirus resistance gene |
Family Cites Families (1)
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| CN1048254C (zh) * | 1993-12-09 | 2000-01-12 | 托马斯杰弗逊大学 | 用于将预定的改变引入靶基因中的化合物 |
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| JP2000509282A (ja) | 2000-07-25 |
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| CN1207302C (zh) | 2005-06-22 |
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| KR20000064969A (ko) | 2000-11-06 |
| US5760012A (en) | 1998-06-02 |
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| EP0906328A1 (en) | 1999-04-07 |
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