ES2139552T1 - Moduladores de la transcripcion regulado por tetraciclinas. - Google Patents

Moduladores de la transcripcion regulado por tetraciclinas.

Info

Publication number
ES2139552T1
ES2139552T1 ES95926605T ES95926605T ES2139552T1 ES 2139552 T1 ES2139552 T1 ES 2139552T1 ES 95926605 T ES95926605 T ES 95926605T ES 95926605 T ES95926605 T ES 95926605T ES 2139552 T1 ES2139552 T1 ES 2139552T1
Authority
ES
Spain
Prior art keywords
tet
linked
tetracicline
analogue
inhibiting
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
ES95926605T
Other languages
English (en)
Other versions
ES2139552T3 (es
Inventor
Hermann Bujard
Manfred Gossen
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
BASF SE
Abbott GmbH and Co KG
Original Assignee
Knoll GmbH
BASF SE
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US08/275,876 external-priority patent/US5654168A/en
Priority claimed from US08/383,754 external-priority patent/US5789156A/en
Application filed by Knoll GmbH, BASF SE filed Critical Knoll GmbH
Publication of ES2139552T1 publication Critical patent/ES2139552T1/es
Application granted granted Critical
Publication of ES2139552T3 publication Critical patent/ES2139552T3/es
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
    • A01K67/027—New or modified breeds of vertebrates
    • A01K67/0275—Genetically modified vertebrates, e.g. transgenic
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/005—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/195—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria
    • C07K14/24—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from bacteria from Enterobacteriaceae (F), e.g. Citrobacter, Serratia, Proteus, Providencia, Morganella, Yersinia
    • C07K14/245—Escherichia (G)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • 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
    • C12N15/62—DNA sequences coding for fusion proteins
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • 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
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • 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
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/635—Externally inducible repressor mediated regulation of gene expression, e.g. tetR inducible by tetracyline
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • 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
    • C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/67—General methods for enhancing the expression
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • 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
    • C12N15/63—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
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • 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
    • C12N15/63—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
    • C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/8509—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells for producing genetically modified animals, e.g. transgenic
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00—Genetically modified animals
    • A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00—Genetically modified animals
    • A01K2217/07—Animals genetically altered by homologous recombination
    • A01K2217/075—Animals genetically altered by homologous recombination inducing loss of function, i.e. knock out
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2217/00—Genetically modified animals
    • A01K2217/20—Animal model comprising regulated expression system
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2227/00—Animals characterised by species
    • A01K2227/10—Mammal
    • A01K2227/105—Murine
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
    • A01K2267/00—Animals characterised by purpose
    • A01K2267/03—Animal model, e.g. for test or diseases
    • A01K2267/0393—Animal model comprising a reporter system for screening tests
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/01—Fusion polypeptide containing a localisation/targetting motif
    • C07K2319/09—Fusion polypeptide containing a localisation/targetting motif containing a nuclear localisation signal
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/61—Fusion polypeptide containing an enzyme fusion for detection (lacZ, luciferase)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/70—Fusion polypeptide containing domain for protein-protein interaction
    • C07K2319/71—Fusion polypeptide containing domain for protein-protein interaction containing domain for transcriptional activaation, e.g. VP16
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • C07K2319/80—Fusion polypeptide containing a DNA binding domain, e.g. Lacl or Tet-repressor
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
    • C12N2710/00011—Details
    • C12N2710/16011—Herpesviridae
    • C12N2710/16611—Simplexvirus, e.g. human herpesvirus 1, 2
    • C12N2710/16622—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2830/00—Vector systems having a special element relevant for transcription
    • C12N2830/001—Vector systems having a special element relevant for transcription controllable enhancer/promoter combination
    • C12N2830/002—Vector systems having a special element relevant for transcription controllable enhancer/promoter combination inducible enhancer/promoter combination, e.g. hypoxia, iron, transcription factor
    • C12N2830/003—Vector systems having a special element relevant for transcription controllable enhancer/promoter combination inducible enhancer/promoter combination, e.g. hypoxia, iron, transcription factor tet inducible
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2830/00—Vector systems having a special element relevant for transcription
    • C12N2830/001—Vector systems having a special element relevant for transcription controllable enhancer/promoter combination
    • C12N2830/005—Vector systems having a special element relevant for transcription controllable enhancer/promoter combination repressible enhancer/promoter combination, e.g. KRAB
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2830/00—Vector systems having a special element relevant for transcription
    • C12N2830/001—Vector systems having a special element relevant for transcription controllable enhancer/promoter combination
    • C12N2830/005—Vector systems having a special element relevant for transcription controllable enhancer/promoter combination repressible enhancer/promoter combination, e.g. KRAB
    • C12N2830/006—Vector systems having a special element relevant for transcription controllable enhancer/promoter combination repressible enhancer/promoter combination, e.g. KRAB tet repressible
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2830/00—Vector systems having a special element relevant for transcription
    • C12N2830/32—Vector systems having a special element relevant for transcription being an silencer not forming part of the promoter region

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  • Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Molecular Biology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Biophysics (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Environmental Sciences (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicinal Chemistry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Veterinary Medicine (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Animal Husbandry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Virology (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Peptides Or Proteins (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

SE PRESENTAN MOLECULAS Y PROTEINAS DE ACIDOS NUCLEICOS UTILES PARA REGULAR LA EXPRESION DE GENES EN CELULAS EUCARIOTICAS Y ORGANISMOS. EN LA INVENCION SE PRESENTA UNA PROTEINA DE FUSION ACTIVADORA TRANSCRIPCIONAL QUE SE ENLAZA A SECUENCIAS OPERADORAS TET Y ESTIMULA LA TRANSCRIPCION DE UN GEN ENLAZADO A UN OPERADOR TET EN PRESENCIA, PERO NO EN AUSENCIA, DE TETRACICLINA (O ANALOGO DE LA MISMA). EN LA INVENCION TAMBIEN SE PRESENTAN PROTEINAS DE FUSION INHIBIDORAS TRANSCRIPCIONALES QUE INHIBEN LA TRANSCRIPCION DE UN GEN ENLAZADO A UN OPERADOR TET DE FORMA CONTROLADA. EN UN ASPECTO DE LA INVENCION, LA PROTEINA DE FUSION INHIBIDORA SE ENLAZA A SECUENCIAS DE OPERADORES TET EN AUSENCIA, PERO NO EN PRESENCIA, DE TETRACICLINA (O ANALOGO DE LA MISMA). EN OTRO ASPECTO DE LA INVENCION, LA PROTEINA DE FUSION INHIBIDORA SE ENLAZA A SECUENCIAS DE OPERADORES TET EN PRESENCIA, PERO NO EN AUSENCIA, DE TETRACICLINA (O ANALOGO DE LA MISMA). LAS PROTEINAS DE FUSION ACTIVADORAS E INHIBIDORAS TRANSCRIPCIONALES DELA INVENCION SE PUEDEN UTILIZAR COMBINADAS PARA REGULAR LA EXPRESION DE UNO O DE MULTIPLES GENES ENLAZADOS A OPERADORES TET. TAMBIEN SE PRESENTAN NUEVAS UNIDADES DE TRANSCRIPCION QUE CONTIENEN OPERADORES TET QUE PERMITEN LA EXPRESION REGULADA POR TETRACICLINA COORDINADA O INDEPENDIENTE DE DOS O MAS GENES MEDIANTE LOS MODULADORES TRANSCRIPCIONALES DE LA INVENCION. TAMBIEN SE PRESENTAN EN LA INVENCION LOS KITS QUE INCLUYEN LOS COMPONENTES DEL SISTEMA REGULADOR.
ES95926605T 1994-07-01 1995-06-29 Moduladores transcripcionales regulados por tetraciclina. Expired - Lifetime ES2139552T3 (es)

Applications Claiming Priority (8)

Application Number Priority Date Filing Date Title
US27063794A 1994-07-01 1994-07-01
US270637 1994-07-01
US275876 1994-07-15
US08/275,876 US5654168A (en) 1994-07-01 1994-07-15 Tetracycline-inducible transcriptional activator and tetracycline-regulated transcription units
US08/383,754 US5789156A (en) 1993-06-14 1995-02-03 Tetracycline-regulated transcriptional inhibitors
US383754 1995-02-03
US08/486,814 US5866755A (en) 1993-06-14 1995-06-07 Animals transgenic for a tetracycline-regulated transcriptional inhibitor
US486814 1995-06-07

Publications (2)

Publication Number Publication Date
ES2139552T1 true ES2139552T1 (es) 2000-02-16
ES2139552T3 ES2139552T3 (es) 2006-04-16

Family

ID=27501005

Family Applications (1)

Application Number Title Priority Date Filing Date
ES95926605T Expired - Lifetime ES2139552T3 (es) 1994-07-01 1995-06-29 Moduladores transcripcionales regulados por tetraciclina.

Country Status (13)

Country Link
US (2) US5866755A (es)
EP (2) EP1092771B1 (es)
JP (3) JP4054058B2 (es)
CN (2) CN1167504A (es)
AT (1) ATE305034T1 (es)
AU (1) AU3092395A (es)
CA (1) CA2193122C (es)
DE (2) DE804565T1 (es)
DK (1) DK0804565T3 (es)
ES (1) ES2139552T3 (es)
FI (1) FI965287A7 (es)
NO (1) NO315375B1 (es)
WO (1) WO1996001313A1 (es)

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US5888981A (en) 1993-06-14 1999-03-30 Basf Aktiengesellschaft Methods for regulating gene expression
CA2165162C (en) 1993-06-14 2000-05-23 Hermann Bujard Tight control of gene expression in eucaryotic cells by tetracycline-responsive promoters
US5859310A (en) 1993-06-14 1999-01-12 Basf Aktiengesellschaft Mice transgenic for a tetracycline-controlled transcriptional activator
US5589362A (en) * 1993-06-14 1996-12-31 Basf Aktiengesellschaft Tetracycline regulated transcriptional modulators with altered DNA binding specificities
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US5851796A (en) * 1995-06-07 1998-12-22 Yale University Autoregulatory tetracycline-regulated system for inducible gene expression in eucaryotes
FR2735789B1 (fr) 1995-06-23 1997-07-25 Centre Nat Rech Scient Adenovirus recombinants, leur utilisation pour preparer des aav, lignee cellulaire complementaire et compositions pharmaceutiques les contenant
GB9526509D0 (en) * 1995-12-23 1996-02-28 Univ Dundee Gene control
DE19635568C1 (de) * 1996-09-02 1998-03-26 Gsf Forschungszentrum Umwelt Vektorsysteme zur konditionalen Genexpression
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WO1998037185A2 (en) * 1997-02-20 1998-08-27 The Board Of Regents Of The University Of Texas System Vectors for controlled gene expression
DE19707493C1 (de) * 1997-02-25 1998-02-26 Univ Ludwigs Albert Nucleinsäurekonstrukte zur lang andauernden Expression von Transgenen
EP0973928B1 (en) 1997-03-11 2010-05-05 Regents Of The University Of Minnesota Dna-based transposon system for the introduction of nucleic acid into dna of a cell
US6638502B1 (en) 1997-04-28 2003-10-28 Gencell Sas Adenovirus-mediated intratumoral delivery of an angiogenesis antagonist for the treatment of tumors
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EP1005486A4 (en) * 1997-08-22 2004-09-29 Univ Washington INDUCIBLE REGULATORY SYSTEMS AND THEIR USE
US5885779A (en) * 1997-09-09 1999-03-23 University Of British Columbia Repressed trans-activator system for characterization of protein-protein interactions
US6576469B1 (en) 1997-09-10 2003-06-10 President And Fellows Of Harvard College Inducible methods for repressing gene function
AU748334B2 (en) 1997-10-16 2002-05-30 Board Of Regents, The University Of Texas System Models and treatments for cardiac hypertrophy in relation with NF-AT3 function
EP1721986A1 (en) * 1997-10-29 2006-11-15 Genetics Institute, LLC Rapid generation of stable mammalian cell lines producing high levels of recombinant proteins
US6136536A (en) * 1997-10-29 2000-10-24 Genetics Institute, Inc. Rapid generation of stable mammalian cell lines producing high levels of recombinant proteins
US5968773A (en) * 1997-11-14 1999-10-19 Heddle; John A. System and method for regulation of gene expression
NZ503859A (en) * 1997-11-18 2003-02-28 Pioneer Hi Bred Int Non-identical minimal recombination sites (FRT) which are non-identical for targeted integration of nucleotide sequences into transformed plants
DE19751587A1 (de) * 1997-11-21 1999-07-29 Hoechst Marion Roussel De Gmbh Onkogen- oder virusgesteuerte Expressionssysteme
US6153383A (en) * 1997-12-09 2000-11-28 Verdine; Gregory L. Synthetic transcriptional modulators and uses thereof
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