WO2001060975A3 - Gene disruption methodologies in fungi for drug target discovery - Google Patents

Gene disruption methodologies in fungi for drug target discovery Download PDF

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Publication number
WO2001060975A3
WO2001060975A3 PCT/US2001/005551 US0105551W WO0160975A3 WO 2001060975 A3 WO2001060975 A3 WO 2001060975A3 US 0105551 W US0105551 W US 0105551W WO 0160975 A3 WO0160975 A3 WO 0160975A3
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WO
WIPO (PCT)
Prior art keywords
genes
essential
gene
allele
development
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/US2001/005551
Other languages
French (fr)
Other versions
WO2001060975A2 (en
Inventor
Terry Roemer
Bo Jiang
Charles Boone
Howard Bussey
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.)
Elitra Pharmaceuticals Inc
Original Assignee
Elitra Pharmaceuticals 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
Application filed by Elitra Pharmaceuticals Inc filed Critical Elitra Pharmaceuticals Inc
Priority to CA002398861A priority Critical patent/CA2398861A1/en
Priority to AU2001243204A priority patent/AU2001243204A1/en
Priority to JP2001560347A priority patent/JP2003523197A/en
Priority to EP01916144A priority patent/EP1292668A2/en
Priority to KR1020027010815A priority patent/KR20020097180A/en
Priority to NZ521037A priority patent/NZ521037A/en
Publication of WO2001060975A2 publication Critical patent/WO2001060975A2/en
Publication of WO2001060975A3 publication Critical patent/WO2001060975A3/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
    • C12N1/00—Microorganisms; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/14—Fungi; Culture media therefor
    • 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
    • C12N15/80—Vectors or expression systems specially adapted for eukaryotic hosts for fungi
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10—Antimycotics
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/37—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from fungi
    • C07K14/39—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from fungi from yeasts
    • C07K14/40—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from fungi from yeasts from Candida
    • 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
    • C12N15/65—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression using markers
    • 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
    • C12N15/87—Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation
    • C12N15/90—Stable introduction of foreign DNA into chromosome
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K2319/00—Fusion polypeptide

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biotechnology (AREA)
  • Biomedical Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Microbiology (AREA)
  • Molecular Biology (AREA)
  • Mycology (AREA)
  • Biophysics (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Medicinal Chemistry (AREA)
  • Oncology (AREA)
  • Botany (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Communicable Diseases (AREA)
  • Public Health (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • General Chemical & Material Sciences (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Virology (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Abstract

The present invention provides methods and compositions that enable the experimental determination as to whether any gene in the genome of a diploid pathogenic organism is essential, and whether it is required for virulence or pathogenicity. The methods involve the construction of genetic mutants in which one allele of a specific gene is inactivated while the other allele of the gene is placed under conditional expression. The identification of essential genes and those genes critical to the development of virulent infections, provides a basis for the development of screens for new drugs against such pathogenic organisms. The present invention further provides ∫i⊃Candida albicans∫/i⊃ genes that are demonstrated to be essential and are potential targets for drug screening. The nucleotide sequence of the target genes can be used for various drug discovery purposes, such as expression of the recombinant protein, hybridization assay and construction of nucleic acid arrays. The uses of proteins encoded by the essential genes, and genetically engineered cells comprising modified alleles of essential genes in various screening methods are also encompassed by the invention.
PCT/US2001/005551 2000-02-18 2001-02-20 Gene disruption methodologies in fungi for drug target discovery Ceased WO2001060975A2 (en)

Priority Applications (6)

Application Number Priority Date Filing Date Title
CA002398861A CA2398861A1 (en) 2000-02-18 2001-02-20 Gene disruption methodologies for drug target discovery
AU2001243204A AU2001243204A1 (en) 2000-02-18 2001-02-20 Gene disruption methodologies for drug target discovery
JP2001560347A JP2003523197A (en) 2000-02-18 2001-02-20 Gene disruption method for drug target search
EP01916144A EP1292668A2 (en) 2000-02-18 2001-02-20 Gene disruption methodologies in fungi for drug target discovery
KR1020027010815A KR20020097180A (en) 2000-02-18 2001-02-20 Gene disruption methodologies for drug target discovery
NZ521037A NZ521037A (en) 2000-02-18 2001-02-20 Gene disruption methodologies for drug target discovery

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US18353400P 2000-02-18 2000-02-18
US60/183,534 2000-02-18

Publications (2)

Publication Number Publication Date
WO2001060975A2 WO2001060975A2 (en) 2001-08-23
WO2001060975A3 true WO2001060975A3 (en) 2002-04-25

Family

ID=22673211

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2001/005551 Ceased WO2001060975A2 (en) 2000-02-18 2001-02-20 Gene disruption methodologies in fungi for drug target discovery

Country Status (7)

Country Link
EP (1) EP1292668A2 (en)
JP (1) JP2003523197A (en)
KR (1) KR20020097180A (en)
AU (1) AU2001243204A1 (en)
CA (1) CA2398861A1 (en)
NZ (1) NZ521037A (en)
WO (1) WO2001060975A2 (en)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030180953A1 (en) * 2000-12-29 2003-09-25 Elitra Pharmaceuticals, Inc. Gene disruption methodologies for drug target discovery
WO2003010333A2 (en) * 2001-07-24 2003-02-06 Affinium Pharmaceuticals Inc. Methods for gene disruption and uses thereof
EP1525302A4 (en) 2002-04-26 2006-01-11 Bristol Myers Squibb Co Novel essential fungal polynucleotides, polypeptides, and methods of use
GB0228702D0 (en) * 2002-12-09 2003-01-15 Oxford Glycosciences Uk Ltd Novel therapeutic target
GB0228694D0 (en) * 2002-12-09 2003-01-15 Oxford Glycosciences Uk Ltd Novel threapeutic target
GB0228704D0 (en) * 2002-12-09 2003-01-15 Oxford Glycosciences Uk Ltd Novel therapeutic target
GB0228697D0 (en) * 2002-12-09 2003-01-15 Oxford Glycosciences Uk Ltd Novel therapeutic target
EP1466974A1 (en) * 2003-04-11 2004-10-13 Max-Delbrück-Centrum Für Molekulare Medizin Inducible site-directed mutagenesis through conditional gene rescue
CN108707554B (en) * 2018-05-21 2021-06-29 河北省农林科学院植物保护研究所 A pair of maize black powder fungus combination and its application
CN115508316B (en) * 2021-06-23 2025-08-26 山东大学 A method for identifying drug-resistant Candida albicans and a kit for identifying the same

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997016540A1 (en) * 1995-11-01 1997-05-09 Millennium Pharmaceuticals, Inc. Chitin synthase 1
WO1999031269A2 (en) * 1997-12-12 1999-06-24 Mcgill University New candida albicans kre9 and uses thereof
WO2000053781A1 (en) * 1999-03-11 2000-09-14 Gpc Biotech, Inc. Generation of conditional yeast mutants, methods and reagents related thereto

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1997016540A1 (en) * 1995-11-01 1997-05-09 Millennium Pharmaceuticals, Inc. Chitin synthase 1
WO1999031269A2 (en) * 1997-12-12 1999-06-24 Mcgill University New candida albicans kre9 and uses thereof
WO2000053781A1 (en) * 1999-03-11 2000-09-14 Gpc Biotech, Inc. Generation of conditional yeast mutants, methods and reagents related thereto

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
GARI ELOI ET AL: "A set of vectors with a tetracycline-regulatable promoter system for modulated gene expression in Saccharomyces cerevisiae", YEAST, CHICHESTER, SUSSEX, GB, vol. 13, no. 9, 1997, pages 837 - 848, XP000926574, ISSN: 0749-503X *
GOW N A R ET AL: "GENES ASSOCIATED WITH DIMORPHISM AND VIRULENCE OF CANDIDA ALBICANS", CANADIAN JOURNAL OF BOTANY, NATIONAL RESEARCH COUNCIL, OTTAWA, CA, vol. 73, no. SUPPL 1, 1995, pages S335 - S342, XP000926595, ISSN: 0008-4026 *
MAO YUXIN ET AL: "Overexpression of a dominant-negative allele of SEC4 inhibits growth and protein secretion in Candida albicans.", JOURNAL OF BACTERIOLOGY, vol. 181, no. 23, December 1999 (1999-12-01), pages 7235 - 7242, XP002180711, ISSN: 0021-9193 *
MENDOZA A ET AL: "Translation elongation factor 2 is encoded by a single essential gene in Candida albicans", GENE, ELSEVIER BIOMEDICAL PRESS. AMSTERDAM, NL, vol. 229, no. 1-2, 18 March 1999 (1999-03-18), pages 183 - 191, XP004161173, ISSN: 0378-1119 *
MIO ET AL: "Cloning of the Candida albicans homolog of Saccharomyces cerevisiae GSC1/ FKS1 and its involvement in beta-1,3-glucan synthesis", JOURNAL OF BACTERIOLOGY, WASHINGTON, DC, US, vol. 179, no. 13, July 1997 (1997-07-01), pages 4096 - 4105, XP002115088, ISSN: 0021-9193 *
MIO TOSHIYUKI ET AL: "Isolation of the Candida albicans homologs of Saccharomyces cerevisiae KRE6 and SKN1: Expression and physiological function", JOURNAL OF BACTERIOLOGY, WASHINGTON, DC, US, vol. 179, no. 7, 1997, pages 2363 - 2372, XP002156281, ISSN: 0021-9193 *

Also Published As

Publication number Publication date
AU2001243204A1 (en) 2001-08-27
CA2398861A1 (en) 2001-08-23
EP1292668A2 (en) 2003-03-19
KR20020097180A (en) 2002-12-31
NZ521037A (en) 2004-09-24
WO2001060975A2 (en) 2001-08-23
JP2003523197A (en) 2003-08-05

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