WO2000049162A3 - Compositions and methods for non-targeted activation of endogenous genes - Google Patents

Compositions and methods for non-targeted activation of endogenous genes Download PDF

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Publication number
WO2000049162A3
WO2000049162A3 PCT/US2000/004429 US0004429W WO0049162A3 WO 2000049162 A3 WO2000049162 A3 WO 2000049162A3 US 0004429 W US0004429 W US 0004429W WO 0049162 A3 WO0049162 A3 WO 0049162A3
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WO
WIPO (PCT)
Prior art keywords
genes
expression
gene
methods
nucleic acid
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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/US2000/004429
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French (fr)
Other versions
WO2000049162A2 (en
WO2000049162A8 (en
Inventor
John J Harrington
Bruce Sherf
Stephen Rundlett
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Athersys Inc
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Athersys Inc
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 US09/276,820 external-priority patent/US6897066B1/en
Priority to BR0008313-5A priority Critical patent/BR0008313A/en
Priority to CA002364267A priority patent/CA2364267A1/en
Priority to IL14496000A priority patent/IL144960A0/en
Priority to HK02101829.3A priority patent/HK1040095A1/en
Priority to EP00908750A priority patent/EP1155131B1/en
Application filed by Athersys Inc filed Critical Athersys Inc
Priority to DE60039585T priority patent/DE60039585D1/en
Priority to JP2000599886A priority patent/JP2004501601A/en
Priority to AU30037/00A priority patent/AU3003700A/en
Publication of WO2000049162A2 publication Critical patent/WO2000049162A2/en
Publication of WO2000049162A3 publication Critical patent/WO2000049162A3/en
Publication of WO2000049162A8 publication Critical patent/WO2000049162A8/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
    • C12N15/10—Processes for the isolation, preparation or purification of DNA or RNA
    • C12N15/1096—Processes for the isolation, preparation or purification of DNA or RNA cDNA Synthesis; Subtracted cDNA library construction, e.g. RT, RT-PCR
    • 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
    • C12N15/67—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
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide
    • 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
    • C12N2800/10—Plasmid DNA
    • C12N2800/108—Plasmid DNA episomal vectors
    • 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
    • C12N2800/20—Pseudochromosomes, minichrosomosomes
    • C12N2800/204—Pseudochromosomes, minichrosomosomes of bacterial origin, e.g. BAC
    • 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
    • C12N2800/60—Vectors containing traps for, e.g. exons, promoters
    • 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
    • C12N2840/00—Vectors comprising a special translation-regulating system
    • C12N2840/20—Vectors comprising a special translation-regulating system translation of more than one cistron
    • 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
    • C12N2840/00—Vectors comprising a special translation-regulating system
    • C12N2840/20—Vectors comprising a special translation-regulating system translation of more than one cistron
    • C12N2840/203—Vectors comprising a special translation-regulating system translation of more than one cistron having an IRES
    • 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
    • C12N2840/00—Vectors comprising a special translation-regulating system
    • C12N2840/44—Vectors comprising a special translation-regulating system being a specific part of the splice mechanism, e.g. donor, acceptor

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  • Health & Medical Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Organic Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Zoology (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Plant Pathology (AREA)
  • Molecular Biology (AREA)
  • Microbiology (AREA)
  • Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Bioinformatics & Computational Biology (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Peptides Or Proteins (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

The present invention is directed generally to activating gene expression or causing over-expression of a gene by recombination methods in situ. The invention also is directed generally to methods for expressing an endogenous gene in a cell at levels higher than those normally found in the cell. In one embodiment of the invention, expression of an endogenous gene is activated or increased following integration into the cell, by non-homologous or illegitimate recombination, of a regulatory sequence that activates expression of the gene. In another embodiment, the expression of the endogenous gene may be further increased by co-integration of one or more amplifiable markers, and selecting for increased copies of the one or more amplifiable markers located on the integrated vector. In another embodiment, the invention is directed to activation of endogenous genes by non-targeted integration of specialized activation vectors, which are provided by the invention, into the genome of a host cell. The invention also provides methods for the identification, activation, isolation, and/or expression of genes undiscoverable by current methods since no target sequence is necessary for integration. The invention also provides methods for isolation of nucleic acid molecules (particularly cDNA molecules) encoding a variety of proteins, including transmembrane proteins, and for isolation of cells expressing such transmembrane proteins which may be heterologous transmembrane proteins. The invention also is directed to isolated genes, gene products, nucleic acid molecules, to compositions comprising such genes, gene products and nucleic acid molecules, and to vectors and host cells comprising such genes and nucleic acid molecules, that may be used in a variety of therapeutic and diagnostic applications. Thus, by the present invention, endogenous genes, including those associated with human disease and development, may be activated and isolated without prior knowledge of the sequence, structure, function, or expression profile of the genes.
PCT/US2000/004429 1999-02-19 2000-02-22 Compositions and methods for non-targeted activation of endogenous genes Ceased WO2000049162A2 (en)

Priority Applications (8)

Application Number Priority Date Filing Date Title
AU30037/00A AU3003700A (en) 1999-02-19 2000-02-22 Compositions and methods for non-targeted activation of endogenous genes
JP2000599886A JP2004501601A (en) 1999-02-19 2000-02-22 Activating compositions and methods of activating endogenous genes without targeting
IL14496000A IL144960A0 (en) 1999-02-19 2000-02-22 Compositions and methods for non-targeted activation of endogenous genes
HK02101829.3A HK1040095A1 (en) 1999-02-19 2000-02-22 Compositions and methods for non-targeted activation of endogenous genes
EP00908750A EP1155131B1 (en) 1999-02-19 2000-02-22 Vector comprising a splice acceptor trap and a poly a trap and the corresponding eukaryotic host cells
BR0008313-5A BR0008313A (en) 1999-02-19 2000-02-22 Compositions and methods for non-directed activation of endogenous genes
DE60039585T DE60039585D1 (en) 1999-02-19 2000-02-22 VECTOR WITH A SPLICE ACCEPTOR TRAP AND A POLY A TRAP AND CORRESPONDING EUKARYOTIC HOST CELLS
CA002364267A CA2364267A1 (en) 1999-02-19 2000-02-22 Compositions and methods for non-targeted activation of endogenous genes

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US25302299A 1999-02-19 1999-02-19
US09/253,022 1999-02-19
US26381499A 1999-03-08 1999-03-08
US09/263,814 1999-03-08
US09/276,820 1999-03-26
US09/276,820 US6897066B1 (en) 1997-09-26 1999-03-26 Compositions and methods for non-targeted activation of endogenous genes

Publications (3)

Publication Number Publication Date
WO2000049162A2 WO2000049162A2 (en) 2000-08-24
WO2000049162A3 true WO2000049162A3 (en) 2000-12-28
WO2000049162A8 WO2000049162A8 (en) 2001-03-01

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2000/004429 Ceased WO2000049162A2 (en) 1999-02-19 2000-02-22 Compositions and methods for non-targeted activation of endogenous genes

Country Status (8)

Country Link
EP (1) EP1155131B1 (en)
JP (1) JP2004501601A (en)
CN (1) CN1384881A (en)
AU (1) AU3003700A (en)
BR (1) BR0008313A (en)
CA (1) CA2364267A1 (en)
IL (1) IL144960A0 (en)
WO (1) WO2000049162A2 (en)

Families Citing this family (15)

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IL135242A0 (en) * 1997-09-26 2001-05-20 Athersys Inc Expression of endogenous genes by non-homologous recombination of a vector construct with cellular dna
US6897066B1 (en) 1997-09-26 2005-05-24 Athersys, Inc. Compositions and methods for non-targeted activation of endogenous genes
WO2001042442A2 (en) 1999-12-10 2001-06-14 Cytos Biotechnology Ag Activation of endogenous genes by genomic introduction of a replicon
US7468242B2 (en) 2001-11-05 2008-12-23 Medgenics, Inc. Dermal micro organs, methods and apparatuses for producing and using the same
US8501396B2 (en) 2001-11-05 2013-08-06 Medgenics Medical Israel Ltd. Dermal micro-organs, methods and apparatuses for producing and using the same
HRP20120673T1 (en) 2003-05-01 2012-10-31 Medgenics, Inc. USE OF DERMAL MICRO-ORGANS
EP1662005A1 (en) * 2004-11-26 2006-05-31 FrankGen Biotechnologie AG Enhancer-containing gene trap vectors for random and targeted gene trapping
AU2006261909B2 (en) * 2005-06-24 2011-08-11 Enteris Biopharma, Inc. Cell lines for expressing enzyme useful in the preparation of amidated products
EP2525808A2 (en) 2010-01-19 2012-11-28 The Trustees Of Columbia University In The City Of New York Osteocalcin as a treatment for male reproductive disorders
WO2014152497A2 (en) 2013-03-15 2014-09-25 The Trustees Of Columbia University In The City Of New York Osteocalcin as a treatment for cognitive disorders
AU2014246731A1 (en) * 2013-03-30 2015-11-19 Usha Biotech Limited Methods and constructs for expressing biologically active proteins in mammalian cells
CN106604994B (en) * 2014-06-23 2021-12-14 通用医疗公司 Genome-wide unbiased identification of DSBs assessed by sequencing (GUIDE-Seq)
JP7175608B2 (en) 2014-11-19 2022-11-21 ザ トラスティーズ オブ コロンビア ユニバーシティ イン ザ シティ オブ ニューヨーク Osteocalcin as a treatment for age-related frailty
EP3448981B1 (en) * 2016-04-30 2022-12-07 Biolegend, Inc. Compositions and methods for performing magnetibuoyant separations
CN111593037B (en) * 2020-06-15 2021-02-09 南通大学 Efficient reptile-derived thrombin and application thereof

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Also Published As

Publication number Publication date
WO2000049162A2 (en) 2000-08-24
AU3003700A (en) 2000-09-04
EP1155131B1 (en) 2008-07-23
IL144960A0 (en) 2002-06-30
CN1384881A (en) 2002-12-11
BR0008313A (en) 2003-09-23
CA2364267A1 (en) 2000-08-24
EP1155131A2 (en) 2001-11-21
WO2000049162A8 (en) 2001-03-01
JP2004501601A (en) 2004-01-22

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