WO2000065076A3 - Synthetic gene for expressing active retroviral protein in eukaryotes - Google Patents

Synthetic gene for expressing active retroviral protein in eukaryotes Download PDF

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Publication number
WO2000065076A3
WO2000065076A3 PCT/EP2000/003765 EP0003765W WO0065076A3 WO 2000065076 A3 WO2000065076 A3 WO 2000065076A3 EP 0003765 W EP0003765 W EP 0003765W WO 0065076 A3 WO0065076 A3 WO 0065076A3
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WO
WIPO (PCT)
Prior art keywords
protein
enzyme
retroviral
gene
integrase
Prior art date
Application number
PCT/EP2000/003765
Other languages
French (fr)
Other versions
WO2000065076A2 (en
Inventor
Zeger Debyser
Clercq Erik De
Peter Cherepanov
Wim Pluymers
Original Assignee
Leuven K U Res & Dev
Zeger Debyser
Clercq Erik De
Peter Cherepanov
Wim Pluymers
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 Leuven K U Res & Dev, Zeger Debyser, Clercq Erik De, Peter Cherepanov, Wim Pluymers filed Critical Leuven K U Res & Dev
Priority to JP2000614410A priority Critical patent/JP2002542791A/en
Priority to CA002369058A priority patent/CA2369058A1/en
Priority to EP00927069A priority patent/EP1183381A2/en
Priority to BR0010077-3A priority patent/BR0010077A/en
Priority to AU45579/00A priority patent/AU778106B2/en
Priority to IL14609000A priority patent/IL146090A0/en
Publication of WO2000065076A2 publication Critical patent/WO2000065076A2/en
Priority to NO20015168A priority patent/NO20015168L/en
Publication of WO2000065076A3 publication Critical patent/WO2000065076A3/en

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    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N7/00Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07KPEPTIDES
    • C07K14/00Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/005Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from viruses
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/63Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
    • C12N15/79Vectors or expression systems specially adapted for eukaryotic hosts
    • C12N15/85Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
    • C12N15/86Viral vectors
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2740/00Reverse transcribing RNA viruses
    • C12N2740/00011Details
    • C12N2740/10011Retroviridae
    • C12N2740/16011Human Immunodeficiency Virus, HIV
    • C12N2740/16041Use of virus, viral particle or viral elements as a vector
    • C12N2740/16043Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2740/00Reverse transcribing RNA viruses
    • C12N2740/00011Details
    • C12N2740/10011Retroviridae
    • C12N2740/16011Human Immunodeficiency Virus, HIV
    • C12N2740/16051Methods of production or purification of viral material
    • C12N2740/16052Methods of production or purification of viral material relating to complementing cells and packaging systems for producing virus or viral particles
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2740/00Reverse transcribing RNA viruses
    • C12N2740/00011Details
    • C12N2740/10011Retroviridae
    • C12N2740/16011Human Immunodeficiency Virus, HIV
    • C12N2740/16111Human Immunodeficiency Virus, HIV concerning HIV env
    • C12N2740/16122New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2800/00Nucleic acids vectors
    • C12N2800/10Plasmid DNA
    • C12N2800/108Plasmid DNA episomal vectors
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2840/00Vectors comprising a special translation-regulating system
    • C12N2840/20Vectors comprising a special translation-regulating system translation of more than one cistron
    • C12N2840/203Vectors comprising a special translation-regulating system translation of more than one cistron having an IRES

Abstract

The present invention features a synthetic gene or region of a gene which has an amended codon usage compared with the wild-type gene and which is for the high level expression of a retroviral protein in eukaryotic cells, the expressed retroviral protein having enzymatic activity in the eukaryotic cell. In addition, the invention features a synthetic gene or region of a gene encoding a retroviral enzyme or part of a retroviral enzyme normally expressed in a mammalian or other eukaryotic cell wherein at least one non-preferred codon in the wild-type gene encoding the enzyme has been replaced by a preferred codon encoding the same amino acid. The retroviral protein may be a protease, reverse transcriptase, integrase protein or a polyprotein gag-pol precursor thereof. In one embodiment the retroviral protein with enzymatic activity is a lentiviral protein. In other embodiments the enzymatically active protein is a pol enzyme. In more preferred embodiments, the enzymatically active protein is a lentiviral integrase. In an even more preferred embodiment the enzyme is an HIV enzyme. In more preferred embodiments the enzymatically active protein is HIV integrase. The present invention also includes a detection method for intracellular integrase using a promoterless reporter gene.
PCT/EP2000/003765 1999-04-26 2000-04-26 Synthetic gene for expressing active retroviral protein in eukaryotes WO2000065076A2 (en)

Priority Applications (7)

Application Number Priority Date Filing Date Title
JP2000614410A JP2002542791A (en) 1999-04-26 2000-04-26 Synthetic genes for expressing active retroviral proteins in eukaryotes
CA002369058A CA2369058A1 (en) 1999-04-26 2000-04-26 Synthetic gene for expressing active retroviral protein in eukaryotes
EP00927069A EP1183381A2 (en) 1999-04-26 2000-04-26 Synthetic gene for expressing active retroviral protein in eukaryotes
BR0010077-3A BR0010077A (en) 1999-04-26 2000-04-26 Synthetic gene for expression of an active retroviral protein in eukaryotes
AU45579/00A AU778106B2 (en) 1999-04-26 2000-04-26 Synthetic gene for expressing active retroviral protein in eukaryotes
IL14609000A IL146090A0 (en) 1999-04-26 2000-04-26 A synthetic gene for expression of a retroviral protein with wild type activity in eukaryotic cells
NO20015168A NO20015168L (en) 1999-04-26 2001-10-23 Synthetic gene for expression of active retroviral protein in eukaryotes

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
EP99201306 1999-04-26
EP99201306.0 2000-01-18
EP00200171 2000-01-18
EP00200171.7 2000-01-18

Publications (2)

Publication Number Publication Date
WO2000065076A2 WO2000065076A2 (en) 2000-11-02
WO2000065076A3 true WO2000065076A3 (en) 2001-12-13

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2000/003765 WO2000065076A2 (en) 1999-04-26 2000-04-26 Synthetic gene for expressing active retroviral protein in eukaryotes

Country Status (11)

Country Link
EP (1) EP1183381A2 (en)
JP (1) JP2002542791A (en)
AU (1) AU778106B2 (en)
BR (1) BR0010077A (en)
CA (1) CA2369058A1 (en)
HU (1) HUP0201019A2 (en)
IL (1) IL146090A0 (en)
NO (1) NO20015168L (en)
PL (1) PL351988A1 (en)
RU (1) RU2001131728A (en)
WO (1) WO2000065076A2 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9598469B2 (en) 2001-07-05 2017-03-21 Novartis Vaccines And Diagnostics, Inc. HIV-1 south african subtype C env proteins

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9803351D0 (en) 1998-02-17 1998-04-15 Oxford Biomedica Ltd Anti-viral vectors
CA2358385C (en) 1998-12-31 2013-08-06 Chiron Corporation Polynucleotides encoding antigenic hiv type c polypeptides, polypeptides and uses thereof
US6656706B2 (en) 1999-12-23 2003-12-02 The United States Of America As Represented By The Department Of Health And Human Services Molecular clones with mutated HIV gag/pol, SIV gag and SIV env genes
EP1246913B1 (en) * 1999-12-23 2009-08-05 The Government of the United States of America, as represented by the Secretary, Department of Health and Human Services Molecular clones with mutated hiv gag/pol, siv gag and siv env genes
AUPQ580300A0 (en) * 2000-02-23 2000-03-16 National Cancer Centre Of Singapore Pte Ltd Genetic analysis
GB0009760D0 (en) * 2000-04-19 2000-06-07 Oxford Biomedica Ltd Method
US6835568B2 (en) 2001-10-30 2004-12-28 Virxsys Corporation Regulated nucleic acid expression system
US7572629B2 (en) 2003-05-06 2009-08-11 National Institute Of Advanced Industrial Science And Technology Multiple gene transcription activity assay system
US8106176B2 (en) * 2005-10-07 2012-01-31 Instituto di Richerche di Biologia Molecolare P. Angeletti SpA Matrix metalloproteinase 11 vaccine
JP6824594B2 (en) 2014-09-11 2021-02-03 Jnc株式会社 How to design synthetic genes

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5434065A (en) * 1993-05-06 1995-07-18 President And Fellows Of Harvard College In vivo selection of microbial virulence genes
US5468629A (en) * 1993-04-13 1995-11-21 Calhoun; Cornelia Method of promoting in vitro homologous recombination transfection in mammalian cells using the RecA protein
WO1997036481A1 (en) * 1996-04-02 1997-10-09 The Regents Of The University Of California Design of novel highly efficient hiv based packaging systems for gene therapy
WO1998012207A1 (en) * 1996-09-20 1998-03-26 The General Hospital Corporation High level expression of proteins
WO1998034640A2 (en) * 1997-02-07 1998-08-13 Merck & Co., Inc. Synthetic hiv gag genes
US5811270A (en) * 1994-05-20 1998-09-22 Grandgenett; Duane P. In vitro method for concerted integration of donor DNA molecules using retroviral integrase proteins
WO2000039302A2 (en) * 1998-12-31 2000-07-06 Chiron Corporation Improved expression of hiv polypeptides and production of virus-like particles

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2358385C (en) * 1998-12-31 2013-08-06 Chiron Corporation Polynucleotides encoding antigenic hiv type c polypeptides, polypeptides and uses thereof

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5468629A (en) * 1993-04-13 1995-11-21 Calhoun; Cornelia Method of promoting in vitro homologous recombination transfection in mammalian cells using the RecA protein
US5434065A (en) * 1993-05-06 1995-07-18 President And Fellows Of Harvard College In vivo selection of microbial virulence genes
US5811270A (en) * 1994-05-20 1998-09-22 Grandgenett; Duane P. In vitro method for concerted integration of donor DNA molecules using retroviral integrase proteins
WO1997036481A1 (en) * 1996-04-02 1997-10-09 The Regents Of The University Of California Design of novel highly efficient hiv based packaging systems for gene therapy
WO1998012207A1 (en) * 1996-09-20 1998-03-26 The General Hospital Corporation High level expression of proteins
WO1998034640A2 (en) * 1997-02-07 1998-08-13 Merck & Co., Inc. Synthetic hiv gag genes
WO2000039302A2 (en) * 1998-12-31 2000-07-06 Chiron Corporation Improved expression of hiv polypeptides and production of virus-like particles

Non-Patent Citations (8)

* Cited by examiner, † Cited by third party
Title
BUSHMAN, F. D. ET AL.: "Retroviral DNA integration directed by HIV integration protein in vitro", SCIENCE, vol. 249, 28 September 1990 (1990-09-28), LANCASTER, PA US, pages 1555 - 1558, XP000953086 *
CHEREPANOV P, SURRATT D, TOELEN J, PLUYMERS W, GRIFFITH J, DE CLERCQ E, DEBYSER Z.: "Activity of recombinant HIV-1 integrase on mini-HIV DNA.", NUCLEIC ACIDS RES. 1999 MAY 15;27(10):2202-10., 15 May 1999 (1999-05-15), XP000877353 *
HAAS J ET AL: "CODON USAGE LIMITATION IN THE EXPRESSION OF HIV-1 ENVELOPE GLYCOPROTEIN", CURRENT BIOLOGY,GB,CURRENT SCIENCE,, vol. 6, no. 3, 1 March 1996 (1996-03-01), pages 315 - 324, XP000619599, ISSN: 0960-9822 *
HOLLER T P ET AL: "HIV1 INTEGRASE EXPRESSED IN ESCHERICHIA COLI FROM A SYNTHETIC GENE", GENE,NL,ELSEVIER BIOMEDICAL PRESS. AMSTERDAM, vol. 136, 22 December 1993 (1993-12-22), pages 323 - 328, XP000199775, ISSN: 0378-1119 *
KATZ, R.A. ET AL.: "The avian retroviral IN protein is both necessary and sufficient for integrative recombination in vitro", CELL, vol. 63, 5 October 1990 (1990-10-05), CELL PRESS, CAMBRIDGE, NA., US, pages 87 - 95, XP000953087, ISSN: 0092-8674 *
KOTSOPOULOU E. ET AL.: "A REV-INDEPENDENT HUMAN IMMUNODEFICINCY VIRUS TYPE 1 (HIV-1)-BASED VECTOR THAT EXPLOITS A CODON OPTIMIZED HIV-1 GAG-POL GENE", JOURNAL OF VIROLOGY., vol. 74, no. 10, May 2000 (2000-05-01), ICAN SOCIETY FOR MICROBIOLOGY US, pages 4839 - 4852, XP002152133 *
SCHNEIDER R ET AL: "Inactivation of the human immunodeficiency virus type 1 inhibitory elements allows rev-independent expression of gag and gag/protease and particle formation", JOURNAL OF VIROLOGY,THE AMERICAN SOCIETY FOR MICROBIOLOGY,US, vol. 71, no. 7, July 1997 (1997-07-01), pages 4892 - 4903, XP002137891, ISSN: 0022-538X *
ZUR MEGEDE J, CHEN MC, DOE B, SCHAEFER M, GREER CE, SELBY M, OTTEN GR, BARNETT SW: "Increased expression and immunogenicity of sequence-modified human immunodeficiency virus type 1 gag gene.", J VIROL 2000 MAR;74(6):2628-35, XP002157414 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9598469B2 (en) 2001-07-05 2017-03-21 Novartis Vaccines And Diagnostics, Inc. HIV-1 south african subtype C env proteins

Also Published As

Publication number Publication date
BR0010077A (en) 2002-01-15
CA2369058A1 (en) 2000-11-02
AU778106B2 (en) 2004-11-18
WO2000065076A2 (en) 2000-11-02
RU2001131728A (en) 2004-02-20
EP1183381A2 (en) 2002-03-06
IL146090A0 (en) 2002-07-25
PL351988A1 (en) 2003-07-14
AU4557900A (en) 2000-11-10
JP2002542791A (en) 2002-12-17
NO20015168D0 (en) 2001-10-23
HUP0201019A2 (en) 2002-08-28
NO20015168L (en) 2001-12-14

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