WO2004035782A3 - Sirna mediated gene silencing in transgenic animals - Google Patents

Sirna mediated gene silencing in transgenic animals Download PDF

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Publication number
WO2004035782A3
WO2004035782A3 PCT/EP2003/011233 EP0311233W WO2004035782A3 WO 2004035782 A3 WO2004035782 A3 WO 2004035782A3 EP 0311233 W EP0311233 W EP 0311233W WO 2004035782 A3 WO2004035782 A3 WO 2004035782A3
Authority
WO
WIPO (PCT)
Prior art keywords
transgenic animals
gene silencing
mediated gene
sirna mediated
sirna
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.)
Ceased
Application number
PCT/EP2003/011233
Other languages
French (fr)
Other versions
WO2004035782A2 (en
Inventor
Jost Seibler
Frieder Schwenk
Ralf Kuehn
Birgit Kueter-Luks
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.)
Artemis Pharmaceuticals GmbH
Original Assignee
Artemis Pharmaceuticals GmbH
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
Application filed by Artemis Pharmaceuticals GmbH filed Critical Artemis Pharmaceuticals GmbH
Priority to CA002502664A priority Critical patent/CA2502664A1/en
Priority to AU2003280356A priority patent/AU2003280356A1/en
Priority to DE60325494T priority patent/DE60325494D1/en
Priority to US10/531,347 priority patent/US20060218654A1/en
Priority to EP03770964A priority patent/EP1551971B1/en
Publication of WO2004035782A2 publication Critical patent/WO2004035782A2/en
Publication of WO2004035782A3 publication Critical patent/WO2004035782A3/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • 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
    • C12N15/111—General methods applicable to biologically active non-coding nucleic acids
    • 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
    • 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
    • C12N15/79—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
    • A01K2217/05—Animals comprising random inserted nucleic acids (transgenic)
    • A01K2217/054—Animals comprising random inserted nucleic acids (transgenic) inducing loss of function
    • A01K2217/058—Animals comprising random inserted nucleic acids (transgenic) inducing loss of function due to expression of inhibitory nucleic acid, e.g. siRNA, antisense
    • 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
    • A01K2227/00—Animals characterised by species
    • A01K2227/40—Fish
    • 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
    • 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
    • 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
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/11—Antisense
    • C12N2310/111—Antisense spanning the whole gene, or a large part of it
    • 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
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
    • 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
    • C12N2330/00—Production
    • C12N2330/30—Production chemically synthesised
    • 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
    • C12N2800/00—Nucleic acids vectors
    • C12N2800/30—Vector systems comprising sequences for excision in presence of a recombinase, e.g. loxP or FRT

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Zoology (AREA)
  • Biotechnology (AREA)
  • Organic Chemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical & Material Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Molecular Biology (AREA)
  • General Health & Medical Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Microbiology (AREA)
  • Biochemistry (AREA)
  • Plant Pathology (AREA)
  • Biophysics (AREA)
  • Veterinary Medicine (AREA)
  • Environmental Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Animal Husbandry (AREA)
  • Biodiversity & Conservation Biology (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Saccharide Compounds (AREA)

Abstract

The present invention relates to a process that enables constitutive and inducible gene knock down in living organisms using a short hairpin RNA expression vector integrated into the genome of the organism.
PCT/EP2003/011233 2002-10-17 2003-10-10 Sirna mediated gene silencing in transgenic animals Ceased WO2004035782A2 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
CA002502664A CA2502664A1 (en) 2002-10-17 2003-10-10 Sirna mediated gene silencing in transgenic animals
AU2003280356A AU2003280356A1 (en) 2002-10-17 2003-10-10 Sirna mediated gene silencing in transgenic animals
DE60325494T DE60325494D1 (en) 2002-10-17 2003-10-10 SIRNA-CONTROLLED GENE EXPRESSION SUPPRESSION IN TRANSGENETIC ANIMALS
US10/531,347 US20060218654A1 (en) 2002-10-17 2003-10-10 Sirna mediated gene silencing in transgenic animals
EP03770964A EP1551971B1 (en) 2002-10-17 2003-10-10 Sirna mediated gene silencing in transgenic animals

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
EP02023283.1 2002-10-17
EP02023283 2002-10-17
US46781403P 2003-05-02 2003-05-02
US60/467,814 2003-05-02
US48596903P 2003-07-10 2003-07-10
US60/485,969 2003-07-10

Publications (2)

Publication Number Publication Date
WO2004035782A2 WO2004035782A2 (en) 2004-04-29
WO2004035782A3 true WO2004035782A3 (en) 2004-05-21

Family

ID=32110519

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2003/011233 Ceased WO2004035782A2 (en) 2002-10-17 2003-10-10 Sirna mediated gene silencing in transgenic animals

Country Status (7)

Country Link
US (1) US20060218654A1 (en)
EP (1) EP1551971B1 (en)
AT (1) ATE418611T1 (en)
AU (1) AU2003280356A1 (en)
CA (1) CA2502664A1 (en)
DE (1) DE60325494D1 (en)
WO (1) WO2004035782A2 (en)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2314687B1 (en) * 2003-01-17 2017-12-27 Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. Inducible small interfering rna (sirna) expression constructs for targeted gene silencing
GB0327585D0 (en) * 2003-11-27 2003-12-31 Genomica Sau Inducible nucleic acid expression system
EP1614755A1 (en) * 2004-07-07 2006-01-11 ARTEMIS Pharmaceuticals GmbH Target transgenesis of short hairpin RNA expression cassette using recombinase mediated cassette exchange
US8137907B2 (en) 2005-01-03 2012-03-20 Cold Spring Harbor Laboratory Orthotopic and genetically tractable non-human animal model for liver cancer and the uses thereof
CA2610265A1 (en) 2005-05-31 2007-05-10 Cold Spring Harbor Laboratory Methods for producing micrornas
WO2007004062A2 (en) * 2005-05-31 2007-01-11 Centre National De La Recherche Scientifique Tetracycline-dependent regulation of rna interference
US20090210955A1 (en) * 2005-06-09 2009-08-20 Artemis Pharmaceuticals Gmbh Shrna and sirna expression in a living organism under control of a codon-optimized repressor gene
EP1731607A1 (en) * 2005-06-09 2006-12-13 ARTEMIS Pharmaceuticals GmbH shRNA and siRNA expression in a living organism under control of a codon-optimized tetracycline repressor gene
US20080220471A1 (en) * 2005-07-27 2008-09-11 Genentech, Inc. Vectors and Methods Using Same
WO2012037547A2 (en) * 2010-09-17 2012-03-22 Mount Sinai School Of Medicine Methods and compositions for inhibiting autophagy for the treatment of fibrosis
WO2014193489A1 (en) * 2013-05-31 2014-12-04 Brandeis University Organic small hairpin rnas
US20170226550A1 (en) * 2014-08-07 2017-08-10 Merck Sharp & Dohme Corp. Inhibitory rna for enhanced protein production in recombinant mammalian cells

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003057840A2 (en) * 2001-12-27 2003-07-17 Allele Biotechnology & Pharmaceuticals, Inc. Compositions for dna mediated gene silencing

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE69940196D1 (en) * 1998-04-15 2009-02-12 Hutchinson Fred Cancer Res METHODS AND VECTOR CONSTRUCTS FOR GENERATING TRANSGENIC RODENTS EXPRESSING A HETEROLOGICAL GENE UBIQUITARY
US20030084471A1 (en) * 2000-03-16 2003-05-01 David Beach Methods and compositions for RNA interference
EP1272630A2 (en) * 2000-03-16 2003-01-08 Genetica, Inc. Methods and compositions for rna interference
CA2499188A1 (en) * 2002-09-27 2004-04-08 Cold Spring Harbor Laboratory Cell-based rna interference and related methods and compositions

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003057840A2 (en) * 2001-12-27 2003-07-17 Allele Biotechnology & Pharmaceuticals, Inc. Compositions for dna mediated gene silencing

Non-Patent Citations (10)

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Title
BRONSON SARAH K ET AL: "Single-copy transgenic mice with chosen-site integration", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES, vol. 93, no. 17, 1996, 1996, pages 9067 - 9072, XP002270939, ISSN: 0027-8424 *
BRUMMELKAMP T R ET AL: "A system for stable expression of short interfering RNAs in mammalian cells", SCIENCE, AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE,, US, vol. 296, no. 5567, 2002, pages 550 - 553, XP002225638, ISSN: 0036-8075 *
DEVROE E & SILVER P A: "Retrovirus-delivered siRNA", BMC TECHNOLOGY, BIOMED CENTRAL, LONDON, GB, 28 August 2002 (2002-08-28), pages 1 - 5, XP002225637, ISSN: 1472-6750 *
HASUWA H ET AL: "Small interfering RNA and gene silencing in transgenic mice and rats", FEBS LETTERS, ELSEVIER SCIENCE PUBLISHERS, AMSTERDAM, NL, vol. 532, no. 1-2, 4 December 2002 (2002-12-04), pages 227 - 230, XP004395375, ISSN: 0014-5793 *
KAWASAKI H ET AL: "Short hairpin type of dsRNAs that are controlled by tRNA Val promoter significantly induce RNAi-mediated gene silencing in the cytoplasm of human cells", NUCLEIC ACIDS RESEARCH, OXFORD UNIVERSITY PRESS, SURREY, GB, vol. 31, no. 2, January 2003 (2003-01-01), pages 700 - 707, XP002965487, ISSN: 0305-1048 *
KISTNER ET AL: "Doxycycline-mediated quantitative and tissue-specific control of gene expression in transgenic mice", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA, NATIONAL ACADEMY OF SCIENCE. WASHINGTON, US, vol. 93, no. 20, October 1996 (1996-10-01), pages 10933 - 10938, XP002110022, ISSN: 0027-8424 *
MATSUKURA SHIRO ET AL: "Establishment of conditional vectors for hairpin siRNA knockdowns.", NUCLEIC ACIDS RESEARCH. ENGLAND 1 AUG 2003, vol. 31, no. 15, 1 August 2003 (2003-08-01), pages (e77) 1 - 5, XP002270940, ISSN: 1362-4962 *
MERLINO G T ET AL: "ACCURATE IN-VITRO TRANSCRIPTIONAL INITIATION OF THE CHICK ALPHA-2 TYPE I COLLAGEN GENE", JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 256, no. 21, 1981, pages 11251 - 11258, XP002270942, ISSN: 0021-9258 *
PAUL C P ET AL: "EFFECTIVE EXPRESSION OF SMALL INTERFERING RNA IN HUMAN CELLS", NATURE BIOTECHNOLOGY, NATURE PUBLISHING, US, vol. 20, no. 5, May 2002 (2002-05-01), pages 505 - 508, XP001121066, ISSN: 1087-0156 *
VAN DE WETERING MARC ET AL: "Specific inhibition of gene expression using a stably integrated, inducible small-interfering-RNA vector.", EMBO REPORTS, vol. 4, no. 6, June 2003 (2003-06-01), pages 609 - 615, XP002270941, ISSN: 1469-221X (ISSN print) *

Also Published As

Publication number Publication date
AU2003280356A1 (en) 2004-05-04
WO2004035782A2 (en) 2004-04-29
CA2502664A1 (en) 2004-04-29
US20060218654A1 (en) 2006-09-28
ATE418611T1 (en) 2009-01-15
DE60325494D1 (en) 2009-02-05
EP1551971A2 (en) 2005-07-13
EP1551971B1 (en) 2008-12-24

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