ES2590343T3 - Composiciones de endorribonucleasas y métodos de uso de las mismas - Google Patents
Composiciones de endorribonucleasas y métodos de uso de las mismas Download PDFInfo
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Abstract
Una endorribonucleasa Csy4 variante que comprende una secuencia de aminoacidos que tiene al menos aproximadamente un 95 % de identidad de secuencia de aminoacidos con la secuencia de aminoacidos de las SEQ ID NO: 101 o la SEQ ID NO: 102 expuestas en la Figura 6, en donde la endorribonucleasa comprende una sustitucion de aminoacido en His29, en donde la endorribonucleasa Csy4 variante es enzimaticamente inactiva en ausencia de imidazol, y en donde la endorribonucleasa Csy4 variante se puede activar en presencia de imidazol.
Description
escinde el polirribonucleótido diana. Una presente endorribonucleasa específica de secuencia enzimáticamente inactiva es útil para aislar un ARN diana de una población mixta de ácidos nucleicos, como se ha descrito anteriormente.
5 En algunas realizaciones, una presente endorribonucleasa específica de secuencia enzimáticamente inactiva comprende una o más sustituciones de aminoácidos en comparación con un polipéptido Csy4, CasE o Cas6 enzimáticamente activo, de origen natural.
En algunas realizaciones, una presente endorribonucleasa específica de secuencia enzimáticamente inactiva comprende una sustitución de aminoácido en His-29 de un polipéptido Csy4 o en una posición equivalente en un polipéptido CasE o Cas6. En algunas realizaciones, una presente endorribonucleasa específica de secuencia enzimáticamente inactiva comprende una sustitución de aminoácido en Ser-148 de un polipéptido Csy4 o en una posición equivalente en un polipéptido CasE o Cas6.
15 La Figura 6 representa ejemplos no limitantes de secuencias de aminoácidos de endorribonucleasa específica de secuencia enzimáticamente inactiva adecuadas. En algunas realizaciones, una presente endorribonucleasa específica de secuencia enzimáticamente inactiva comprende una secuencia de aminoácidos que tiene al menos aproximadamente un 75 %, al menos aproximadamente un 80 %, al menos aproximadamente un 85 %, al menos aproximadamente un 90 %, al menos aproximadamente un 95 %, al menos aproximadamente un 98 %, al menos aproximadamente un 99 % o un 100 % de identidad de secuencia de aminoácidos con una secuencia de aminoácidos representada en la Figura 6 donde la secuencia de aminoácidos incluye la sustitución en His-29, Ser50 o tanto His-29 como Ser-50. Por ejemplo, la endorribonucleasa Csy4 variante puede incluir una sustitución H29A (His-29 a Ala-29), una sustitución S50C (Ser-50 a Cys-50) o tanto una sustitución H29A como S50C.
25 En algunas realizaciones, una presente endorribonucleasa específica de secuencia enzimáticamente inactiva es una endorribonucleasa Csy4 variante. En algunas realizaciones una presente endorribonucleasa Csy4 variante comprende una secuencia de aminoácidos que tiene al menos aproximadamente un 95 % de identidad de secuencia de aminoácidos con la secuencia de aminoácidos expuesta en la Figura 6, donde la endorribonucleasa comprende una sustitución de aminoácidos en His-29, donde la endorribonucleasa Csy4 variante es enzimáticamente inactiva en ausencia de imidazol, y donde la endorribonucleasa Csy4 variante se puede activar en presencia de imidazol. En algunos casos, la sustitución de aminoácidos es una sustitución His-29 a Ala-29. En algunos casos, la endorribonucleasa Csy4 variante también incluye una sustitución Ser-50. En algunos casos, una presente endorribonucleasa Csy4 variante se une a un sustrato de ARN que comprende la secuencia de nucleótidos 5'-GUUCACUGCCGUAUAGGCAGCUAAGAAA-3' (SEQ ID NO: 1).
35 Una presente endorribonucleasa específica de secuencia enzimáticamente inactiva es enzimáticamente inactiva "de forma condicional", por ejemplo, una presente endorribonucleasa específica de secuencia enzimáticamente inactiva (por ejemplo, una presente endorribonucleasa Csy4 variante) es enzimáticamente inactiva en ausencia de imidazol; y la endorribonucleasa específica de secuencia enzimáticamente inactiva (por ejemplo, la presente endorribonucleasa Csy4 variante) se puede activar por imidazol. Por ejemplo, la endorribonucleasa específica de secuencia enzimáticamente inactiva (por ejemplo, la presente endorribonucleasa Csy4 variante) puede activarse enzimáticamente por contacto de la endorribonucleasa con imidazol a una concentración de aproximadamente 100 mM a aproximadamente 500 mM.
45 La presencia de imidazol (por ejemplo en un intervalo de concentración de aproximadamente 100 mM a aproximadamente 500 mM) reactiva la endorribonucleasa enzimáticamente inactiva específica de secuencia de modo que la endorribonucleasa queda enzimáticamente activa, por ejemplo, la endorribonucleasa muestra al menos aproximadamente un 50 %, al menos aproximadamente un 60 %, al menos aproximadamente un 70 %, al menos aproximadamente un 80 %, al menos aproximadamente un 90 %, al menos aproximadamente un 95 % o más del 95 % de la endorribonucleasa específica de secuencia de tipo silvestre (por ejemplo, una secuencia de aminoácidos presentada en la Figura 5 (por ejemplo, SEQ ID NO: 6, 8 o 9)).
En algunas realizaciones, una presente endorribonucleasa específica de secuencia enzimáticamente inactiva (por ejemplo, una presente endorribonucleasa Csy4 variante) comprende un marcador detectable, incluyendo un resto
55 que proporciona una señal detectable. Los marcadores y/o restos detectables adecuados que proporcionan una señal detectable incluyen, aunque sin limitación, una enzima, un radioisótopo, un miembro de un par FRET, un miembro de un par de unión específico; un fluoróforo; una proteína fluorescente; un punto cuántico; y similares.
Los pares FRET (donante/aceptor) adecuados para su uso incluyen, aunque sin limitación, EDANS/fluoresceína, IAEDANS/fluoresceína, fluoresceína/tetrametilrrodamina, fluoresceína/Cy 5, IEDANS/DABCYL, fluoresceína/QSY-7, fluoresceína/LC rojo 640, fluoresceína/Cy 5.5 y fluoresceína/LC rojo 705. Además, puede usarse un par donante/aceptor de fluoróforo/punto cuántico.
Los fluoróforos ("marcador fluorescente") adecuados incluyen cualquier molécula que pueda detectarse mediante
65 sus propiedades fluorescentes inherentes, que incluyen fluorescencia detectable tras excitación. Los marcadores fluorescentes adecuados incluyen, aunque sin limitación, fluoresceína, rodamina, tetrametilrrodamina, eosina,
11
eritrosina, cumarina, metilcumarina, pireno, verde Malaquita, estilbeno, amarillo Lucifer, Cascade Blue™, rojo Texas, IAEDANS, EDANS, BODIPY FL, LC rojo 640, Cy 5, Cy 5.5, LC rojo 705 y verde Oregón. Se describen colorantes ópticos adecuados en el 2002 Molecular Probes Handbook, 9ª Ed., de Richard P. Haugland.
5 Las enzimas adecuadas incluyen, aunque sin limitación, peroxidasa de rábano rusticano, luciferasa, β-galactosidasa y similares.
Las proteínas fluorescentes adecuadas incluyen, aunque sin limitación, una proteína fluorescente verde (GFP), por ejemplo, una GFP de Aequoria victoria o un mutante o derivado de la misma, por ejemplo, como se describe en las
10 patentes de Estados Unidos n.º 6.066.476; 6.020.192; 5.985.577; 5.976.796; 5.968.750; 5.968.738; 5.958.713; 5.919.445; 5.874.304; una proteína fluorescente roja; una proteína fluorescente amarilla; cualquiera de diversas proteínas fluorescentes y coloreadas de especies de antozoos, como se describe en, por ejemplo, Matz et al. (1999) Nature Biotechnol. 17:969-973; y similares.
15 Nanopartículas adecuadas incluyen, por ejemplo, punto cuántico (QD), nanopartículas fluorescentes o luminiscentes y nanopartículas magnéticas. Puede detectarse cualquier propiedad óptica o magnética o característica de la nanopartícula o nanopartículas.
Los QD y métodos para su síntesis son bien conocidos en la técnica (véanse, por ejemplo, las patentes de Estados
20 Unidos n.º 6.322.901; 6.576.291; y 6.815.064). Los QD pueden volverse solubles en agua aplicando capas de recubrimiento que comprenden diversos materiales diferentes (véanse, por ejemplo, las patentes de Estados Unidos n.º 6.423.551; 6.251.303; 6.319.426; 6.426.513; 6.444.143; y 6.649.138). Por ejemplo, los QD pueden solubilizarse usando polímeros anfífilos. Los polímeros a modo de ejemplo que se han empleado incluyen ácido poliacrílico de bajo peso molecular modificado con octilamina, fosfolípidos derivatizados con polietilenglicol (PEG), polianhídridos,
25 copolímeros de bloque, etc. Los QD pueden conjugarse a un polipéptido mediante cualquiera de varios grupos funcionales diferentes o agentes de unión que pueden unirse directa o indirectamente a una capa de recubrimiento (véanse, por ejemplo, las patentes de Estados Unidos n.º 5.990.479; 6.207.392; 6.251.303; 6.306.610; 6.325.144; y 6.423.551).
30 Los QD con una amplia diversidad de espectros de absorción y emisión están disponibles en el mercado, por ejemplo, en Quantum Dot Corp. (Hayward Calif.; ahora propiedad de Invitrogen) o en Evident Technologies (Troy, N.Y.). Por ejemplo, están disponibles QD que tienen longitudes de onda de emisión máximas de aproximadamente 525, 535, 545, 565, 585, 605, 655, 705, y 800 nm. Por tanto, los QD pueden tener un intervalo de diferentes colores a través de la parte visible del espectro y en algunos casos incluso más allá.
35 1251, y 131I. El
Los radioisótopos adecuados incluyen, aunque sin limitación, 14C, 3H, 32P, 33P, 35S, uso de radioisótopos como marcadores es bien conocido en la técnica.
En algunas realizaciones, una presente endorribonucleasa específica de secuencia enzimáticamente inactiva (por
40 ejemplo, una presente endorribonucleasa Csy4 variante) se inmoviliza sobre un sustrato insoluble. Los sustratos insolubles adecuados incluyen, aunque sin limitación, perlas de agarosa, perlas magnéticas, una tira de ensayo, una placa multipocillo y similares. El sustrato insoluble puede comprender diversas sustancias (vidrio, poliestireno, cloruro de polivinilo, polipropileno, polietileno, policarbonato, dextrano, nylon, amilosa, celulosas naturales y modificadas, poliacrilamidas, agarosas, y magnetita) y puede proporcionarse en diversas formas, incluyendo, por
45 ejemplo, perlas de agarosas, perlas de poliestireno, perlas de látex, perlas magnéticas, partículas de metal coloide, chips y superficies de vidrio y/o silicio, tiras de nitrocelulosa, membranas de nylon, láminas, pocillos de placas de reacción (por ejemplo, placas multipocillo), tubos de plástico, etc.
En algunas realizaciones, una presente endorribonucleasa específica de secuencia enzimáticamente inactiva (por
50 ejemplo, una presente endorribonucleasa Csy4 variante) se purifica, por ejemplo, es al menos un 80 % pura, al menos un 85 % pura, al menos un 90 % pura, al menos un 95 % pura, al menos un 98 % pura, al menos un 99 % pura o más del 99 % pura.
Composiciones
55 La presente descripción proporciona composiciones que comprenden una presente endorribonucleasa enzimáticamente inactiva específica de secuencia. Una presente composición puede comprender, además de una presente endorribonucleasa enzimáticamente inactiva específica de secuencia, uno o más de: una sal, por ejemplo, NaCl, MgCl, KCl, MgSO4, etc.; un agente tamponante, por ejemplo, un tampón Tris, ácido N-(2-hidroxietil)piperazina
60 N'-(2-etanosulfónico) (HEPES), ácido 2-(N-morfolino)etanosulfónico (MES), sal sódica del ácido 2-(Nmorfolino)etanosulfónico (MES), ácido 3-(N-morfolino)propanosulfónico (MOPS), ácido N-tris[hidroximetil]metil-3aminopropanosulfónico (TAPS), etc.; un agente solubilizante; un detergente, por ejemplo, un detergente no iónico tal como Tween-20, etc.; un inhibidor de proteasa; y similares.
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Applications Claiming Priority (7)
Application Number | Priority Date | Filing Date | Title |
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US33316310P | 2010-05-10 | 2010-05-10 | |
US333163P | 2010-05-10 | ||
US36562710P | 2010-07-19 | 2010-07-19 | |
US365627P | 2010-07-19 | ||
US41328710P | 2010-11-12 | 2010-11-12 | |
US413287P | 2010-11-12 | ||
PCT/US2011/035775 WO2011143124A2 (en) | 2010-05-10 | 2011-05-09 | Endoribonuclease compositions and methods of use thereof |
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ES2590343T3 true ES2590343T3 (es) | 2016-11-21 |
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EP (2) | EP2569425B1 (es) |
JP (1) | JP5926242B2 (es) |
KR (1) | KR101867359B1 (es) |
CN (1) | CN103038338B (es) |
AU (1) | AU2011253222B2 (es) |
BR (1) | BR112012028805A2 (es) |
CA (1) | CA2798703A1 (es) |
DK (1) | DK2569425T3 (es) |
EA (1) | EA024121B9 (es) |
ES (1) | ES2590343T3 (es) |
MX (1) | MX2012013037A (es) |
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CA2798703A1 (en) | 2010-05-10 | 2011-11-17 | The Regents Of The University Of California | Endoribonuclease compositions and methods of use thereof |
EP3613852A3 (en) | 2011-07-22 | 2020-04-22 | President and Fellows of Harvard College | Evaluation and improvement of nuclease cleavage specificity |
US11021737B2 (en) | 2011-12-22 | 2021-06-01 | President And Fellows Of Harvard College | Compositions and methods for analyte detection |
GB201122458D0 (en) | 2011-12-30 | 2012-02-08 | Univ Wageningen | Modified cascade ribonucleoproteins and uses thereof |
PT2800811T (pt) | 2012-05-25 | 2017-08-17 | Univ California | Métodos e composições para modificação de adn alvo dirigida por arn e para modulação dirigida por arn de transcrição |
WO2013188037A2 (en) * | 2012-06-11 | 2013-12-19 | Agilent Technologies, Inc | Method of adaptor-dimer subtraction using a crispr cas6 protein |
WO2013188638A2 (en) * | 2012-06-15 | 2013-12-19 | The Regents Of The University Of California | Endoribonucleases and methods of use thereof |
CA2877290A1 (en) | 2012-06-19 | 2013-12-27 | Daniel F. Voytas | Gene targeting in plants using dna viruses |
EP3494997B1 (en) | 2012-07-25 | 2019-09-18 | The Broad Institute, Inc. | Inducible dna binding proteins and genome perturbation tools and applications thereof |
WO2014022702A2 (en) | 2012-08-03 | 2014-02-06 | The Regents Of The University Of California | Methods and compositions for controlling gene expression by rna processing |
CN110643600A (zh) * | 2012-10-23 | 2020-01-03 | 基因工具股份有限公司 | 用于切割靶dna的系统及其用途 |
ES2769310T3 (es) | 2012-12-06 | 2020-06-25 | Sigma Aldrich Co Llc | Modificación y regulación del genoma basada en CRISPR |
US8697359B1 (en) | 2012-12-12 | 2014-04-15 | The Broad Institute, Inc. | CRISPR-Cas systems and methods for altering expression of gene products |
EP3825401A1 (en) | 2012-12-12 | 2021-05-26 | The Broad Institute, Inc. | Crispr-cas component systems, methods and compositions for sequence manipulation |
EP4279588A3 (en) | 2012-12-12 | 2024-01-17 | The Broad Institute, Inc. | Engineering of systems, methods and optimized guide compositions for sequence manipulation |
MX2015007550A (es) | 2012-12-12 | 2017-02-02 | Broad Inst Inc | Suministro, modificación y optimización de sistemas, métodos y composiciones para la manipulación de secuencias y aplicaciones terapéuticas. |
WO2014093655A2 (en) | 2012-12-12 | 2014-06-19 | The Broad Institute, Inc. | Engineering and optimization of systems, methods and compositions for sequence manipulation with functional domains |
EP2931892B1 (en) | 2012-12-12 | 2018-09-12 | The Broad Institute, Inc. | Methods, models, systems, and apparatus for identifying target sequences for cas enzymes or crispr-cas systems for target sequences and conveying results thereof |
SG10201912327SA (en) | 2012-12-12 | 2020-02-27 | Broad Inst Inc | Engineering and Optimization of Improved Systems, Methods and Enzyme Compositions for Sequence Manipulation |
US20140310830A1 (en) | 2012-12-12 | 2014-10-16 | Feng Zhang | CRISPR-Cas Nickase Systems, Methods And Compositions For Sequence Manipulation in Eukaryotes |
EP3553174A1 (en) | 2012-12-17 | 2019-10-16 | President and Fellows of Harvard College | Rna-guided human genome engineering |
EP3578666A1 (en) | 2013-03-12 | 2019-12-11 | President and Fellows of Harvard College | Method of generating a three-dimensional nucleic acid containing matrix |
ES2901396T3 (es) | 2013-03-14 | 2022-03-22 | Caribou Biosciences Inc | Composiciones y métodos de ácidos nucleicos dirigidos a ácido nucleico |
CN110540991B (zh) | 2013-03-15 | 2023-10-24 | 通用医疗公司 | 使用截短的引导RNA(tru-gRNA)提高RNA引导的基因组编辑的特异性 |
US10760064B2 (en) | 2013-03-15 | 2020-09-01 | The General Hospital Corporation | RNA-guided targeting of genetic and epigenomic regulatory proteins to specific genomic loci |
WO2014204578A1 (en) | 2013-06-21 | 2014-12-24 | The General Hospital Corporation | Using rna-guided foki nucleases (rfns) to increase specificity for rna-guided genome editing |
US9902973B2 (en) | 2013-04-11 | 2018-02-27 | Caribou Biosciences, Inc. | Methods of modifying a target nucleic acid with an argonaute |
MY177814A (en) | 2013-06-04 | 2020-09-23 | Harvard College | Rna-guided transcriptional regulation |
US9267135B2 (en) | 2013-06-04 | 2016-02-23 | President And Fellows Of Harvard College | RNA-guided transcriptional regulation |
EP3011034B1 (en) | 2013-06-17 | 2019-08-07 | The Broad Institute, Inc. | Delivery, use and therapeutic applications of the crispr-cas systems and compositions for targeting disorders and diseases using viral components |
AU2014281026B2 (en) | 2013-06-17 | 2020-05-28 | Massachusetts Institute Of Technology | Delivery, engineering and optimization of tandem guide systems, methods and compositions for sequence manipulation |
WO2014204727A1 (en) | 2013-06-17 | 2014-12-24 | The Broad Institute Inc. | Functional genomics using crispr-cas systems, compositions methods, screens and applications thereof |
RU2716420C2 (ru) | 2013-06-17 | 2020-03-11 | Те Брод Инститьют Инк. | Доставка и применение систем crispr-cas, векторов и композиций для целенаправленного воздействия и терапии в печени |
CN105492611A (zh) | 2013-06-17 | 2016-04-13 | 布罗德研究所有限公司 | 用于序列操纵的优化的crispr-cas双切口酶系统、方法以及组合物 |
BR112016000571B1 (pt) | 2013-07-10 | 2023-12-26 | President And Fellows Of Harvard College | Métodos in vitro para modular a expressão e para alterar um ou mais ácidos nucleicos alvo em uma célula simultaneamente com a regulação da expressão de um ou mais ácidos nucleicos alvo em uma célula, bem como célula de levedura ou bactéria compreendendo ácidos nucleicos |
US10563225B2 (en) | 2013-07-26 | 2020-02-18 | President And Fellows Of Harvard College | Genome engineering |
US9163284B2 (en) | 2013-08-09 | 2015-10-20 | President And Fellows Of Harvard College | Methods for identifying a target site of a Cas9 nuclease |
MX2016002118A (es) | 2013-08-22 | 2016-06-28 | Du Pont | Modificacion del genoma de plantas por medio del uso de sistemas de ácido ribonucléico (arn) guía/ endonucleasa cas y metodos de uso. |
US9359599B2 (en) | 2013-08-22 | 2016-06-07 | President And Fellows Of Harvard College | Engineered transcription activator-like effector (TALE) domains and uses thereof |
US9228207B2 (en) | 2013-09-06 | 2016-01-05 | President And Fellows Of Harvard College | Switchable gRNAs comprising aptamers |
US9737604B2 (en) | 2013-09-06 | 2017-08-22 | President And Fellows Of Harvard College | Use of cationic lipids to deliver CAS9 |
US9322037B2 (en) | 2013-09-06 | 2016-04-26 | President And Fellows Of Harvard College | Cas9-FokI fusion proteins and uses thereof |
WO2015040402A1 (en) | 2013-09-18 | 2015-03-26 | Kymab Limited | Methods. cells & organisms |
WO2015048707A2 (en) * | 2013-09-30 | 2015-04-02 | Regents Of The University Of Minnesota | Conferring resistance to geminiviruses in plants using crispr/cas systems |
WO2015065964A1 (en) | 2013-10-28 | 2015-05-07 | The Broad Institute Inc. | Functional genomics using crispr-cas systems, compositions, methods, screens and applications thereof |
AU2014346559B2 (en) | 2013-11-07 | 2020-07-09 | Editas Medicine,Inc. | CRISPR-related methods and compositions with governing gRNAs |
US10787684B2 (en) | 2013-11-19 | 2020-09-29 | President And Fellows Of Harvard College | Large gene excision and insertion |
US9074199B1 (en) | 2013-11-19 | 2015-07-07 | President And Fellows Of Harvard College | Mutant Cas9 proteins |
US20150166982A1 (en) | 2013-12-12 | 2015-06-18 | President And Fellows Of Harvard College | Methods for correcting pi3k point mutations |
WO2015089486A2 (en) | 2013-12-12 | 2015-06-18 | The Broad Institute Inc. | Systems, methods and compositions for sequence manipulation with optimized functional crispr-cas systems |
CN105899657A (zh) | 2013-12-12 | 2016-08-24 | 布罗德研究所有限公司 | 用于改变基因产物表达的crispr-cas系统和方法、结构信息以及诱导型模块化cas酶 |
WO2015089364A1 (en) | 2013-12-12 | 2015-06-18 | The Broad Institute Inc. | Crystal structure of a crispr-cas system, and uses thereof |
MX2016007328A (es) | 2013-12-12 | 2017-07-19 | Broad Inst Inc | Suministro, uso y aplicaciones terapeuticas de sistemas y composiciones crispr-cas para edicion del genoma. |
AU2014362248A1 (en) | 2013-12-12 | 2016-06-16 | Massachusetts Institute Of Technology | Compositions and methods of use of CRISPR-Cas systems in nucleotide repeat disorders |
EP3985124A1 (en) * | 2013-12-26 | 2022-04-20 | The General Hospital Corporation | Multiplex guide rnas |
EP3957735A1 (en) | 2014-03-05 | 2022-02-23 | Editas Medicine, Inc. | Crispr/cas-related methods and compositions for treating usher syndrome and retinitis pigmentosa |
US11141493B2 (en) | 2014-03-10 | 2021-10-12 | Editas Medicine, Inc. | Compositions and methods for treating CEP290-associated disease |
US11339437B2 (en) | 2014-03-10 | 2022-05-24 | Editas Medicine, Inc. | Compositions and methods for treating CEP290-associated disease |
WO2015138510A1 (en) | 2014-03-10 | 2015-09-17 | Editas Medicine., Inc. | Crispr/cas-related methods and compositions for treating leber's congenital amaurosis 10 (lca10) |
EP3981876A1 (en) | 2014-03-26 | 2022-04-13 | Editas Medicine, Inc. | Crispr/cas-related methods and compositions for treating sickle cell disease |
AU2015280069B2 (en) | 2014-06-23 | 2021-08-12 | The General Hospital Corporation | Genomewide unbiased identification of dsbs evaluated by sequencing (guide-seq) |
AU2015288157A1 (en) | 2014-07-11 | 2017-01-19 | E. I. Du Pont De Nemours And Company | Compositions and methods for producing plants resistant to glyphosate herbicide |
US10077453B2 (en) | 2014-07-30 | 2018-09-18 | President And Fellows Of Harvard College | CAS9 proteins including ligand-dependent inteins |
US10435685B2 (en) | 2014-08-19 | 2019-10-08 | Pacific Biosciences Of California, Inc. | Compositions and methods for enrichment of nucleic acids |
EP3186376B1 (en) | 2014-08-27 | 2019-03-20 | Caribou Biosciences, Inc. | Methods for increasing cas9-mediated engineering efficiency |
CN108064129A (zh) | 2014-09-12 | 2018-05-22 | 纳幕尔杜邦公司 | 玉米和大豆中复合性状基因座的位点特异性整合位点的产生和使用方法 |
US10040048B1 (en) | 2014-09-25 | 2018-08-07 | Synthego Corporation | Automated modular system and method for production of biopolymers |
EP3985115A1 (en) | 2014-12-12 | 2022-04-20 | The Broad Institute, Inc. | Protected guide rnas (pgrnas) |
ES2955957T3 (es) | 2015-01-28 | 2023-12-11 | Caribou Biosciences Inc | Polinucleótidos de ADN/ARN híbridos CRISPR y procedimientos de uso |
EP3265559B1 (en) | 2015-03-03 | 2021-01-06 | The General Hospital Corporation | Engineered crispr-cas9 nucleases with altered pam specificity |
WO2016149547A1 (en) | 2015-03-17 | 2016-09-22 | Bio-Rad Laboratories, Inc. | Detection of genome editing |
EP3553178A1 (en) | 2015-03-27 | 2019-10-16 | E. I. du Pont de Nemours and Company | Soybean u6 small nuclear rna gene promoters and their use in constitutive expression of small rna genes in plants |
CN107690480B (zh) | 2015-04-24 | 2022-03-22 | 爱迪塔斯医药公司 | Cas9分子/指导rna分子复合物的评价 |
US20180296537A1 (en) | 2015-06-05 | 2018-10-18 | Novartis Ag | Methods and compositions for diagnosing, treating, and monitoring treatment of shank3 deficiency associated disorders |
US20160362667A1 (en) | 2015-06-10 | 2016-12-15 | Caribou Biosciences, Inc. | CRISPR-Cas Compositions and Methods |
WO2016205759A1 (en) | 2015-06-18 | 2016-12-22 | The Broad Institute Inc. | Engineering and optimization of systems, methods, enzymes and guide scaffolds of cas9 orthologs and variants for sequence manipulation |
RU2752834C2 (ru) | 2015-06-18 | 2021-08-09 | Те Брод Инститьют, Инк. | Мутации фермента crispr, уменьшающие нецелевые эффекты |
US9580727B1 (en) | 2015-08-07 | 2017-02-28 | Caribou Biosciences, Inc. | Compositions and methods of engineered CRISPR-Cas9 systems using split-nexus Cas9-associated polynucleotides |
US9926546B2 (en) | 2015-08-28 | 2018-03-27 | The General Hospital Corporation | Engineered CRISPR-Cas9 nucleases |
WO2017040348A1 (en) | 2015-08-28 | 2017-03-09 | The General Hospital Corporation | Engineered crispr-cas9 nucleases |
US9512446B1 (en) | 2015-08-28 | 2016-12-06 | The General Hospital Corporation | Engineered CRISPR-Cas9 nucleases |
AU2016319110B2 (en) | 2015-09-11 | 2022-01-27 | The General Hospital Corporation | Full interrogation of nuclease DSBs and sequencing (FIND-seq) |
JP2018529353A (ja) | 2015-09-30 | 2018-10-11 | ザ ジェネラル ホスピタル コーポレイション | 配列決定法による切断事象の包括的生体外報告(CIRCLE−seq) |
IL294014B1 (en) | 2015-10-23 | 2024-03-01 | Harvard College | Nucleobase editors and their uses |
DK3350327T3 (en) | 2015-10-23 | 2019-01-21 | Caribou Biosciences Inc | CONSTRUCTED CRISPR CLASS-2-NUCLEIC ACID TARGETING-NUCLEIC ACID |
AU2016349288A1 (en) | 2015-11-03 | 2018-05-31 | President And Fellows Of Harvard College | Method and apparatus for volumetric imaging of a three-dimensional nucleic acid containing matrix |
AU2016363024B2 (en) | 2015-12-04 | 2020-01-30 | Caribou Biosciences, Inc. | Engineered nucleic-acid targeting nucleic acids |
WO2017139309A1 (en) | 2016-02-12 | 2017-08-17 | Ceres, Inc. | Methods and materials for high throughput testing of mutagenized allele combinations |
WO2017165862A1 (en) | 2016-03-25 | 2017-09-28 | Editas Medicine, Inc. | Systems and methods for treating alpha 1-antitrypsin (a1at) deficiency |
WO2017189525A1 (en) | 2016-04-25 | 2017-11-02 | President And Fellows Of Harvard College | Hybridization chain reaction methods for in situ molecular detection |
US10266851B2 (en) | 2016-06-02 | 2019-04-23 | Sigma-Aldrich Co. Llc | Using programmable DNA binding proteins to enhance targeted genome modification |
US11293021B1 (en) | 2016-06-23 | 2022-04-05 | Inscripta, Inc. | Automated cell processing methods, modules, instruments, and systems |
AU2017305404B2 (en) | 2016-08-02 | 2023-11-30 | Editas Medicine, Inc. | Compositions and methods for treating CEP290 associated disease |
AU2017306676B2 (en) | 2016-08-03 | 2024-02-22 | President And Fellows Of Harvard College | Adenosine nucleobase editors and uses thereof |
CA3033327A1 (en) | 2016-08-09 | 2018-02-15 | President And Fellows Of Harvard College | Programmable cas9-recombinase fusion proteins and uses thereof |
WO2018039438A1 (en) | 2016-08-24 | 2018-03-01 | President And Fellows Of Harvard College | Incorporation of unnatural amino acids into proteins using base editing |
CN110214180A (zh) | 2016-10-14 | 2019-09-06 | 哈佛大学的校长及成员们 | 核碱基编辑器的aav递送 |
EP3525832A4 (en) | 2016-10-14 | 2020-04-29 | The General Hospital Corp. | SITE SPECIFIC NUCLEASES WITH EPIGENETIC REGULATION |
US9816093B1 (en) | 2016-12-06 | 2017-11-14 | Caribou Biosciences, Inc. | Engineered nucleic acid-targeting nucleic acids |
WO2018119359A1 (en) | 2016-12-23 | 2018-06-28 | President And Fellows Of Harvard College | Editing of ccr5 receptor gene to protect against hiv infection |
US11898179B2 (en) | 2017-03-09 | 2024-02-13 | President And Fellows Of Harvard College | Suppression of pain by gene editing |
JP2020510439A (ja) | 2017-03-10 | 2020-04-09 | プレジデント アンド フェローズ オブ ハーバード カレッジ | シトシンからグアニンへの塩基編集因子 |
EP3596217A1 (en) | 2017-03-14 | 2020-01-22 | Editas Medicine, Inc. | Systems and methods for the treatment of hemoglobinopathies |
KR20190130613A (ko) | 2017-03-23 | 2019-11-22 | 프레지던트 앤드 펠로우즈 오브 하바드 칼리지 | 핵산 프로그램가능한 dna 결합 단백질을 포함하는 핵염기 편집제 |
KR20200006054A (ko) | 2017-04-12 | 2020-01-17 | 더 브로드 인스티튜트, 인코퍼레이티드 | 신규 타입 vi crispr 오르소로그 및 시스템 |
EP3612551A4 (en) | 2017-04-21 | 2020-12-30 | The General Hospital Corporation | VARIANTS OF CPF1 (CAS12A) WITH MODIFIED PAM SPECIFICITY |
EP3622070A2 (en) | 2017-05-10 | 2020-03-18 | Editas Medicine, Inc. | Crispr/rna-guided nuclease systems and methods |
WO2018209320A1 (en) | 2017-05-12 | 2018-11-15 | President And Fellows Of Harvard College | Aptazyme-embedded guide rnas for use with crispr-cas9 in genome editing and transcriptional activation |
JP2020521446A (ja) | 2017-05-25 | 2020-07-27 | ザ ジェネラル ホスピタル コーポレイション | 二部塩基エディター(bbe)構造およびii型−c−cas9ジンクフィンガー編集 |
US9982279B1 (en) | 2017-06-23 | 2018-05-29 | Inscripta, Inc. | Nucleic acid-guided nucleases |
US10011849B1 (en) | 2017-06-23 | 2018-07-03 | Inscripta, Inc. | Nucleic acid-guided nucleases |
HRP20220615T1 (hr) | 2017-06-30 | 2022-06-24 | Inscripta, Inc. | Postupci, moduli, instrumenti i sustavi za automatiziranu obradu stanica |
WO2019023680A1 (en) | 2017-07-28 | 2019-01-31 | President And Fellows Of Harvard College | METHODS AND COMPOSITIONS FOR EVOLUTION OF BASIC EDITORS USING PHAGE-ASSISTED CONTINUOUS EVOLUTION (PACE) |
WO2019040650A1 (en) | 2017-08-23 | 2019-02-28 | The General Hospital Corporation | GENETICALLY MODIFIED CRISPR-CAS9 NUCLEASES HAVING MODIFIED PAM SPECIFICITY |
US10738327B2 (en) | 2017-08-28 | 2020-08-11 | Inscripta, Inc. | Electroporation cuvettes for automation |
US11319532B2 (en) | 2017-08-30 | 2022-05-03 | President And Fellows Of Harvard College | High efficiency base editors comprising Gam |
CA3074927A1 (en) | 2017-09-30 | 2019-04-04 | Inscripta, Inc. | Flow through electroporation instrumentation |
US11725228B2 (en) | 2017-10-11 | 2023-08-15 | The General Hospital Corporation | Methods for detecting site-specific and spurious genomic deamination induced by base editing technologies |
US11795443B2 (en) | 2017-10-16 | 2023-10-24 | The Broad Institute, Inc. | Uses of adenosine base editors |
US11661599B1 (en) | 2017-12-14 | 2023-05-30 | National Technology & Engineering Solutions Of Sandia, Llc | CRISPR-Cas based system for targeting single-stranded sequences |
US20190233816A1 (en) | 2018-01-26 | 2019-08-01 | Massachusetts Institute Of Technology | Structure-guided chemical modification of guide rna and its applications |
CN108486098B (zh) * | 2018-03-06 | 2021-07-06 | 中山大学肿瘤防治中心(中山大学附属肿瘤医院、中山大学肿瘤研究所) | 一种用SLFN13从总RNA中纯化总mRNA的方法 |
CN112204131A (zh) | 2018-03-29 | 2021-01-08 | 因思科瑞普特公司 | 用于诱导和转化的细胞生长速率的自动化控制 |
US10376889B1 (en) | 2018-04-13 | 2019-08-13 | Inscripta, Inc. | Automated cell processing instruments comprising reagent cartridges |
WO2019204378A1 (en) | 2018-04-17 | 2019-10-24 | The General Hospital Corporation | Sensitive in vitro assays for substrate preferences and sites of nucleic acid binding, modifying, and cleaving agents |
US10557216B2 (en) | 2018-04-24 | 2020-02-11 | Inscripta, Inc. | Automated instrumentation for production of T-cell receptor peptide libraries |
WO2019209926A1 (en) | 2018-04-24 | 2019-10-31 | Inscripta, Inc. | Automated instrumentation for production of peptide libraries |
US10858761B2 (en) | 2018-04-24 | 2020-12-08 | Inscripta, Inc. | Nucleic acid-guided editing of exogenous polynucleotides in heterologous cells |
US10227576B1 (en) | 2018-06-13 | 2019-03-12 | Caribou Biosciences, Inc. | Engineered cascade components and cascade complexes |
IL292273B2 (en) | 2018-08-14 | 2023-10-01 | Inscripta Inc | Devices, modules and methods for improved detection of edited sequences in living cells |
US10532324B1 (en) | 2018-08-14 | 2020-01-14 | Inscripta, Inc. | Instruments, modules, and methods for improved detection of edited sequences in live cells |
US11142740B2 (en) | 2018-08-14 | 2021-10-12 | Inscripta, Inc. | Detection of nuclease edited sequences in automated modules and instruments |
US10752874B2 (en) | 2018-08-14 | 2020-08-25 | Inscripta, Inc. | Instruments, modules, and methods for improved detection of edited sequences in live cells |
EP3844263A4 (en) | 2018-08-30 | 2022-05-25 | Inscripta, Inc. | ENHANCED DETECTION OF NUCLEASE-EDITED SEQUENCES IN AUTOMATED MODULES AND INSTRUMENTS |
US11214781B2 (en) | 2018-10-22 | 2022-01-04 | Inscripta, Inc. | Engineered enzyme |
WO2020086475A1 (en) | 2018-10-22 | 2020-04-30 | Inscripta, Inc. | Engineered enzymes |
WO2020123887A2 (en) | 2018-12-14 | 2020-06-18 | Pioneer Hi-Bred International, Inc. | Novel crispr-cas systems for genome editing |
US11946040B2 (en) | 2019-02-04 | 2024-04-02 | The General Hospital Corporation | Adenine DNA base editor variants with reduced off-target RNA editing |
EP3942040A1 (en) | 2019-03-19 | 2022-01-26 | The Broad Institute, Inc. | Methods and compositions for editing nucleotide sequences |
US11001831B2 (en) | 2019-03-25 | 2021-05-11 | Inscripta, Inc. | Simultaneous multiplex genome editing in yeast |
CN113631713A (zh) | 2019-03-25 | 2021-11-09 | 因思科瑞普特公司 | 酵母中的同时多重基因组编辑 |
RU2707542C1 (ru) | 2019-03-28 | 2019-11-27 | Федеральное бюджетное учреждение науки "Центральный научно-исследовательский институт эпидемиологии" Федеральной службы по надзору в сфере защиты прав потребителей и благополучия человека (ФБУН ЦНИИ Эпидемиологии Роспотребнадзора) | Способ получения препарата рекомбинантной нуклеазы CAS, по существу, свободного от бактериальных эндотоксинов, полученный данным способом препарат и содержащий его набор для использования в системе CRISPR/Cas |
CA3139122C (en) | 2019-06-06 | 2023-04-25 | Inscripta, Inc. | Curing for recursive nucleic acid-guided cell editing |
US10907125B2 (en) | 2019-06-20 | 2021-02-02 | Inscripta, Inc. | Flow through electroporation modules and instrumentation |
CN114008070A (zh) | 2019-06-21 | 2022-02-01 | 因思科瑞普特公司 | 导致大肠杆菌赖氨酸产量增加的全基因组合理设计的突变 |
US10927385B2 (en) | 2019-06-25 | 2021-02-23 | Inscripta, Inc. | Increased nucleic-acid guided cell editing in yeast |
US11767524B2 (en) * | 2019-09-24 | 2023-09-26 | Abclonal Science, Inc. | His-MBP tagged DNA endonuclease for facilitated enzyme removal |
WO2021102059A1 (en) | 2019-11-19 | 2021-05-27 | Inscripta, Inc. | Methods for increasing observed editing in bacteria |
WO2021118626A1 (en) | 2019-12-10 | 2021-06-17 | Inscripta, Inc. | Novel mad nucleases |
US10704033B1 (en) | 2019-12-13 | 2020-07-07 | Inscripta, Inc. | Nucleic acid-guided nucleases |
KR20220118498A (ko) | 2019-12-18 | 2022-08-25 | 인스크립타 인코포레이티드 | 핵산-가이드된 뉴클레아제 편집된 세포의 생체 내 검출을 위한 캐스케이드/dcas3 상보 검정 |
US10689669B1 (en) | 2020-01-11 | 2020-06-23 | Inscripta, Inc. | Automated multi-module cell processing methods, instruments, and systems |
AU2021213705A1 (en) | 2020-01-27 | 2022-06-16 | Inscripta, Inc. | Electroporation modules and instrumentation |
US20210332388A1 (en) | 2020-04-24 | 2021-10-28 | Inscripta, Inc. | Compositions, methods, modules and instruments for automated nucleic acid-guided nuclease editing in mammalian cells |
MX2022014008A (es) | 2020-05-08 | 2023-02-09 | Broad Inst Inc | Métodos y composiciones para la edición simultánea de ambas cadenas de una secuencia de nucleótidos de doble cadena objetivo. |
US11787841B2 (en) | 2020-05-19 | 2023-10-17 | Inscripta, Inc. | Rationally-designed mutations to the thrA gene for enhanced lysine production in E. coli |
WO2022060749A1 (en) | 2020-09-15 | 2022-03-24 | Inscripta, Inc. | Crispr editing to embed nucleic acid landing pads into genomes of live cells |
US11512297B2 (en) | 2020-11-09 | 2022-11-29 | Inscripta, Inc. | Affinity tag for recombination protein recruitment |
EP4271802A1 (en) | 2021-01-04 | 2023-11-08 | Inscripta, Inc. | Mad nucleases |
WO2022150269A1 (en) | 2021-01-07 | 2022-07-14 | Inscripta, Inc. | Mad nucleases |
US11884924B2 (en) | 2021-02-16 | 2024-01-30 | Inscripta, Inc. | Dual strand nucleic acid-guided nickase editing |
WO2023004391A2 (en) | 2021-07-21 | 2023-01-26 | Montana State University | Nucleic acid detection using type iii crispr complex |
US20230279442A1 (en) | 2021-12-15 | 2023-09-07 | Versitech Limited | Engineered cas9-nucleases and method of use thereof |
CN114410635B (zh) * | 2022-03-29 | 2022-06-14 | 中国科学院天津工业生物技术研究所 | 威尼斯镰刀菌内源U6启动子及其基于CRISPR/Cas9的基因编辑方法 |
CN115976080B (zh) * | 2022-11-28 | 2024-04-19 | 南方医科大学南方医院 | 一种鉴定与人脑lncRNA互作蛋白的载体及其应用 |
Family Cites Families (53)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5034506A (en) | 1985-03-15 | 1991-07-23 | Anti-Gene Development Group | Uncharged morpholino-based polymers having achiral intersubunit linkages |
US5585362A (en) | 1989-08-22 | 1996-12-17 | The Regents Of The University Of Michigan | Adenovirus vectors for gene therapy |
US5489677A (en) | 1990-07-27 | 1996-02-06 | Isis Pharmaceuticals, Inc. | Oligonucleoside linkages containing adjacent oxygen and nitrogen atoms |
US5602240A (en) | 1990-07-27 | 1997-02-11 | Ciba Geigy Ag. | Backbone modified oligonucleotide analogs |
CA2115742A1 (en) | 1991-08-20 | 1993-03-04 | Ronald G. Crystal | Adenovirus mediated transfer of genes to the gastrointestinal tract |
US5252479A (en) | 1991-11-08 | 1993-10-12 | Research Corporation Technologies, Inc. | Safe vector for gene therapy |
FR2688514A1 (fr) | 1992-03-16 | 1993-09-17 | Centre Nat Rech Scient | Adenovirus recombinants defectifs exprimant des cytokines et medicaments antitumoraux les contenant. |
AU680459B2 (en) | 1992-12-03 | 1997-07-31 | Genzyme Corporation | Gene therapy for cystic fibrosis |
JP3532566B2 (ja) | 1993-06-24 | 2004-05-31 | エル. グラハム,フランク | 遺伝子治療のためのアデノウイルスベクター |
DE69434594T2 (de) | 1993-10-25 | 2006-09-21 | Canji, Inc., San Diego | Rekombinante adenoviren-vektor und verfahren zur verwendung |
US5625048A (en) | 1994-11-10 | 1997-04-29 | The Regents Of The University Of California | Modified green fluorescent proteins |
WO1996017951A2 (en) | 1994-12-09 | 1996-06-13 | Rpms Technology Limited | Identification of genes responsible for in vivo survival of microorganisms |
US5958713A (en) | 1995-01-31 | 1999-09-28 | Novo Nordisk A/S | Method of detecting biologically active substances by using green fluorescent protein |
US5968738A (en) | 1995-12-06 | 1999-10-19 | The Board Of Trustees Of The Leland Stanford Junior University | Two-reporter FACS analysis of mammalian cells using green fluorescent proteins |
US5874304A (en) | 1996-01-18 | 1999-02-23 | University Of Florida Research Foundation, Inc. | Humanized green fluorescent protein genes and methods |
US6020192A (en) | 1996-01-18 | 2000-02-01 | University Of Florida | Humanized green fluorescent protein genes and methods |
US5976796A (en) | 1996-10-04 | 1999-11-02 | Loma Linda University | Construction and expression of renilla luciferase and green fluorescent protein fusion genes |
TW371617B (en) | 1996-10-09 | 1999-10-11 | Of Animal And Plant Health Inspection And Quarantine Council Of Agriculture Executive Yuan Bureau | Method to transplant GFP into autographa californica multiple nuclear polyhedrosis virus for inflicting pest in an attempt to detect and flow up it existence and to improve life span against UV |
US6080849A (en) | 1997-09-10 | 2000-06-27 | Vion Pharmaceuticals, Inc. | Genetically modified tumor-targeted bacteria with reduced virulence |
US6322901B1 (en) | 1997-11-13 | 2001-11-27 | Massachusetts Institute Of Technology | Highly luminescent color-selective nano-crystalline materials |
US6207392B1 (en) | 1997-11-25 | 2001-03-27 | The Regents Of The University Of California | Semiconductor nanocrystal probes for biological applications and process for making and using such probes |
US5990479A (en) | 1997-11-25 | 1999-11-23 | Regents Of The University Of California | Organo Luminescent semiconductor nanocrystal probes for biological applications and process for making and using such probes |
US6306610B1 (en) | 1998-09-18 | 2001-10-23 | Massachusetts Institute Of Technology | Biological applications of quantum dots |
US6251303B1 (en) | 1998-09-18 | 2001-06-26 | Massachusetts Institute Of Technology | Water-soluble fluorescent nanocrystals |
US6426513B1 (en) | 1998-09-18 | 2002-07-30 | Massachusetts Institute Of Technology | Water-soluble thiol-capped nanocrystals |
US5985577A (en) | 1998-10-14 | 1999-11-16 | The Trustees Of Columbia University In The City Of New York | Protein conjugates containing multimers of green fluorescent protein |
US6325144B1 (en) | 2000-06-09 | 2001-12-04 | Baker Hughes, Inc. | Inflatable packer with feed-thru conduits |
US6649138B2 (en) | 2000-10-13 | 2003-11-18 | Quantum Dot Corporation | Surface-modified semiconductive and metallic nanoparticles having enhanced dispersibility in aqueous media |
US6576291B2 (en) | 2000-12-08 | 2003-06-10 | Massachusetts Institute Of Technology | Preparation of nanocrystallites |
GB0105924D0 (en) | 2001-03-09 | 2001-04-25 | Microscience Ltd | Promoter |
AU2002306849A1 (en) | 2001-03-21 | 2002-10-08 | Elitra Pharmaceuticals, Inc. | Identification of essential genes in microorganisms |
CA2453450A1 (en) | 2001-07-20 | 2003-11-06 | Quantum Dot Corporation | Luminescent nanoparticles and methods for their preparation |
US7268229B2 (en) | 2001-11-02 | 2007-09-11 | Promega Corporation | Compounds to co-localize luminophores with luminescent proteins |
CN103937827A (zh) | 2003-06-13 | 2014-07-23 | 新泽西内科与牙科大学 | Rna干扰酶及其使用方法 |
WO2005074986A2 (en) | 2004-02-10 | 2005-08-18 | Genobiotix Aps | Bioactive species capable of interfering with a microbial toxin-antitoxin complex and methods for evaluation and use of said bioactive species |
US7919277B2 (en) | 2004-04-28 | 2011-04-05 | Danisco A/S | Detection and typing of bacterial strains |
JPWO2006123537A1 (ja) * | 2005-05-16 | 2008-12-25 | タカラバイオ株式会社 | 新規なエンドリボヌクレア−ゼ |
WO2007013265A1 (ja) | 2005-07-26 | 2007-02-01 | Takara Bio Inc. | 新規なエンドリボヌクレアーゼ |
US10066233B2 (en) | 2005-08-26 | 2018-09-04 | Dupont Nutrition Biosciences Aps | Method of modulating cell resistance |
CN101268186B (zh) * | 2005-09-21 | 2011-08-03 | 宝生物工程株式会社 | 新的内切核糖核酸酶 |
EP2426220B1 (en) | 2006-05-19 | 2016-06-22 | DuPont Nutrition Biosciences ApS | Tagged microorganisms and methods of tagging |
US8431698B2 (en) | 2007-08-29 | 2013-04-30 | Biolume Inc. | Bioluminescent endoscopy methods and compounds |
US8546553B2 (en) | 2008-07-25 | 2013-10-01 | University Of Georgia Research Foundation, Inc. | Prokaryotic RNAi-like system and methods of use |
WO2010054108A2 (en) * | 2008-11-06 | 2010-05-14 | University Of Georgia Research Foundation, Inc. | Cas6 polypeptides and methods of use |
WO2010054154A2 (en) | 2008-11-07 | 2010-05-14 | Danisco A/S | Bifidobacteria crispr sequences |
WO2010066907A1 (en) | 2008-12-12 | 2010-06-17 | Danisco A/S | Genetic cluster of strains of streptococcus thermophilus having unique rheological properties for dairy fermentation |
CA2798703A1 (en) | 2010-05-10 | 2011-11-17 | The Regents Of The University Of California | Endoribonuclease compositions and methods of use thereof |
WO2012164565A1 (en) | 2011-06-01 | 2012-12-06 | Yeda Research And Development Co. Ltd. | Compositions and methods for downregulating prokaryotic genes |
CA3226329A1 (en) | 2011-12-16 | 2013-06-20 | Targetgene Biotechnologies Ltd | Compositions and methods for modifying a predetermined target nucleic acid sequence |
GB201122458D0 (en) | 2011-12-30 | 2012-02-08 | Univ Wageningen | Modified cascade ribonucleoproteins and uses thereof |
WO2013141680A1 (en) | 2012-03-20 | 2013-09-26 | Vilnius University | RNA-DIRECTED DNA CLEAVAGE BY THE Cas9-crRNA COMPLEX |
US9637739B2 (en) | 2012-03-20 | 2017-05-02 | Vilnius University | RNA-directed DNA cleavage by the Cas9-crRNA complex |
WO2014022702A2 (en) | 2012-08-03 | 2014-02-06 | The Regents Of The University Of California | Methods and compositions for controlling gene expression by rna processing |
-
2011
- 2011-05-09 CA CA2798703A patent/CA2798703A1/en not_active Abandoned
- 2011-05-09 BR BR112012028805A patent/BR112012028805A2/pt not_active IP Right Cessation
- 2011-05-09 EA EA201291024A patent/EA024121B9/ru not_active IP Right Cessation
- 2011-05-09 EP EP11781086.1A patent/EP2569425B1/en not_active Not-in-force
- 2011-05-09 WO PCT/US2011/035775 patent/WO2011143124A2/en active Application Filing
- 2011-05-09 EP EP16167704.2A patent/EP3078753B1/en not_active Not-in-force
- 2011-05-09 KR KR1020127031818A patent/KR101867359B1/ko active IP Right Grant
- 2011-05-09 SG SG2012082426A patent/SG185481A1/en unknown
- 2011-05-09 DK DK11781086.1T patent/DK2569425T3/en active
- 2011-05-09 MX MX2012013037A patent/MX2012013037A/es active IP Right Grant
- 2011-05-09 CN CN201180033802.7A patent/CN103038338B/zh not_active Expired - Fee Related
- 2011-05-09 AU AU2011253222A patent/AU2011253222B2/en not_active Ceased
- 2011-05-09 ES ES11781086.1T patent/ES2590343T3/es active Active
- 2011-05-09 JP JP2013510211A patent/JP5926242B2/ja not_active Expired - Fee Related
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- 2012-11-07 US US13/671,120 patent/US9115348B2/en active Active
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US20170166958A1 (en) | 2017-06-15 |
KR20130079420A (ko) | 2013-07-10 |
EP2569425B1 (en) | 2016-07-06 |
US9115348B2 (en) | 2015-08-25 |
EP2569425A2 (en) | 2013-03-20 |
US20130130248A1 (en) | 2013-05-23 |
SG185481A1 (en) | 2012-12-28 |
JP5926242B2 (ja) | 2016-05-25 |
KR101867359B1 (ko) | 2018-07-23 |
EP3078753A1 (en) | 2016-10-12 |
EA024121B1 (ru) | 2016-08-31 |
JP2013528372A (ja) | 2013-07-11 |
MX2012013037A (es) | 2013-07-29 |
US20150284697A1 (en) | 2015-10-08 |
BR112012028805A2 (pt) | 2019-09-24 |
EP3078753B1 (en) | 2018-04-18 |
CA2798703A1 (en) | 2011-11-17 |
WO2011143124A2 (en) | 2011-11-17 |
EP2569425A4 (en) | 2014-03-12 |
WO2011143124A3 (en) | 2012-04-19 |
US9708646B2 (en) | 2017-07-18 |
AU2011253222A1 (en) | 2012-12-06 |
CN103038338A (zh) | 2013-04-10 |
EA024121B9 (ru) | 2017-01-30 |
US9605246B2 (en) | 2017-03-28 |
CN103038338B (zh) | 2017-03-08 |
AU2011253222B2 (en) | 2014-08-21 |
EA201291024A1 (ru) | 2013-11-29 |
DK2569425T3 (en) | 2016-10-03 |
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