WO2001083736A3 - Internal de novo initiation sites of the hcv ns5b polymerase and use thereof - Google Patents

Internal de novo initiation sites of the hcv ns5b polymerase and use thereof Download PDF

Info

Publication number
WO2001083736A3
WO2001083736A3 PCT/CA2001/000580 CA0100580W WO0183736A3 WO 2001083736 A3 WO2001083736 A3 WO 2001083736A3 CA 0100580 W CA0100580 W CA 0100580W WO 0183736 A3 WO0183736 A3 WO 0183736A3
Authority
WO
WIPO (PCT)
Prior art keywords
initiation
poly
utr
novo
internal
Prior art date
Application number
PCT/CA2001/000580
Other languages
French (fr)
Other versions
WO2001083736A2 (en
Inventor
Charles Pellerin
George Kukolj
Original Assignee
Boehringer Ingelheim Ca Ltd
Charles Pellerin
George Kukolj
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 Boehringer Ingelheim Ca Ltd, Charles Pellerin, George Kukolj filed Critical Boehringer Ingelheim Ca Ltd
Priority to EP01927534A priority Critical patent/EP1278837A2/en
Priority to AU2001254563A priority patent/AU2001254563A1/en
Publication of WO2001083736A2 publication Critical patent/WO2001083736A2/en
Publication of WO2001083736A3 publication Critical patent/WO2001083736A3/en

Links

Classifications

    • 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
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/10—Transferases (2.)
    • C12N9/12—Transferases (2.) transferring phosphorus containing groups, e.g. kinases (2.7)
    • C12N9/1241—Nucleotidyltransferases (2.7.7)
    • C12N9/127—RNA-directed RNA polymerase (2.7.7.48), i.e. RNA replicase
    • 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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • 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
    • C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
    • C12N2770/00011—Details
    • C12N2770/24011—Flaviviridae
    • C12N2770/24211—Hepacivirus, e.g. hepatitis C virus, hepatitis G virus
    • 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
    • C12N2770/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA ssRNA viruses positive-sense
    • C12N2770/00011—Details
    • C12N2770/24011—Flaviviridae
    • C12N2770/24211—Hepacivirus, e.g. hepatitis C virus, hepatitis G virus
    • C12N2770/24222—New viral proteins or individual genes, new structural or functional aspects of known viral proteins or genes

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Microbiology (AREA)
  • Biophysics (AREA)
  • Medicinal Chemistry (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Virology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Abstract

To further define the nature of de novo initiation from the 3'-UTR, several distinct 3'-UTR's that harbor the conserved terminal 98 nucleotides, but have poly U/U-C tracts of different length were isolated and characterized. Reconstitution of de novo initiation by the mature NS5B with the different 3'-UTR RNA substrates revealed distinctively sized products that are consistent with internal initiation at specific sites within the polypyrimidine tract. These sites were mapped by demonstrating that nucleotide substitutions of the cytidylate residues in the poly U/U-C template affect the generation of specific products of the de novo initiation reaction. Moreover, initiation within the poly U/U-C template is also primed by GTP and an assay that evaluates inhibitors of this reaction as potential HCV therapeutics is claimed.
PCT/CA2001/000580 2000-04-21 2001-04-20 Internal de novo initiation sites of the hcv ns5b polymerase and use thereof WO2001083736A2 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP01927534A EP1278837A2 (en) 2000-04-21 2001-04-20 Internal de novo initiation sites of the hcv ns5b polymerase and use thereof
AU2001254563A AU2001254563A1 (en) 2000-04-21 2001-04-20 Internal de novo initiation sites of the hcv ns5b polymerase and use thereof

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US19879300P 2000-04-21 2000-04-21
US60/198,793 2000-04-21

Publications (2)

Publication Number Publication Date
WO2001083736A2 WO2001083736A2 (en) 2001-11-08
WO2001083736A3 true WO2001083736A3 (en) 2002-08-01

Family

ID=22734870

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CA2001/000580 WO2001083736A2 (en) 2000-04-21 2001-04-20 Internal de novo initiation sites of the hcv ns5b polymerase and use thereof

Country Status (4)

Country Link
US (1) US20010055756A1 (en)
EP (1) EP1278837A2 (en)
AU (1) AU2001254563A1 (en)
WO (1) WO2001083736A2 (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2363483A3 (en) 2004-03-05 2014-07-16 Benitec, Inc. Multiple promoter expression cassettes for simultaneous delivery of RNAi agents
FR2901807B1 (en) * 2006-05-30 2013-08-23 Univ Victor Segalen Bordeaux 2 NEW TREATMENT OF HCV INFECTION
US9775894B2 (en) 2013-07-09 2017-10-03 University Of Washington Through Its Center For Commercialization Methods and compositions for activation of innate immune responses through RIG-I like receptor signaling

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998039031A1 (en) * 1997-03-04 1998-09-11 Washington University Functional dna clone for hepatitis c virus (hcv) and uses thereof
WO2000033635A2 (en) * 1998-12-10 2000-06-15 Eli Lilly And Company Primer-independent rna synthesis catalyzed by hcv polymerase

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998039031A1 (en) * 1997-03-04 1998-09-11 Washington University Functional dna clone for hepatitis c virus (hcv) and uses thereof
WO2000033635A2 (en) * 1998-12-10 2000-06-15 Eli Lilly And Company Primer-independent rna synthesis catalyzed by hcv polymerase

Non-Patent Citations (12)

* Cited by examiner, † Cited by third party
Title
C. CHENG KAO ET AL: "Template Requirements for RNA Synthesis by a recombinant Hepatitis C virus RNA-dependent RNA polymerase", JOURNAL OF VIROLOGY., vol. 74, no. 23, December 2000 (2000-12-01), THE AMERICAN SOCIETY FOR MICROBIOLOGY., US, pages 11121 - 11128, XP002194351, ISSN: 0022-538X *
G. LUO ET AL: "De Novo initiation of RNA synthesis by RNA-dependent NA Polymerase (NS5B) of hepatitis virus", JOURNAL OF VIROLOGY., vol. 74, no. 2, January 2000 (2000-01-01), THE AMERICAN SOCIETY FOR MICROBIOLOGY., US, pages 851 - 863, XP002194348, ISSN: 0022-538X *
HONG ZHI ET AL: "A novel mechanism to ensure terminal initiation by hepatitis C virus NS5B polymerase.", VIROLOGY, vol. 285, no. 1, 20 June 2001 (2001-06-20), pages 6 - 11, XP002194353, ISSN: 0042-6822 *
JONG-WON OH ET AL: "A recombinant hepatitis C virus RNA-dependent RNA polymerase capable of copying the full-length viral RNA", JOURNAL OF VIROLOGY., vol. 73, no. 9, September 1999 (1999-09-01), THE AMERICAN SOCIETY FOR MICROBIOLOGY., US, pages 7694 - 7702, XP002194349, ISSN: 0022-538X *
JONG-WON OH ET AL: "Template requirement and initiation site selection by hepatitis c virus polymerase on a minimal viral RNA template", JOURNAL OF BIOLOGICAL CHEMISTRY., vol. 275, no. 23, 9 June 2000 (2000-06-09), AMERICAN SOCIETY OF BIOLOGICAL CHEMISTS, BALTIMORE, MD., US, pages 17710 - 17717, XP002194350, ISSN: 0021-9258 *
KAO C C ET AL: "De novo initiation of RNA synthesis by a recombinant flaviridae RNA-dependent RNA polymerase", VIROLOGY, ACADEMIC PRESS,ORLANDO, US, vol. 253, 1999, pages 1 - 7, XP002110174, ISSN: 0042-6822 *
KOLYKHALOV A A ET AL: "IDENTIFICATION OF A HIGHLY CONSERVED SEQUENCE ELEMENT AT THE 3' TERMINUS OF HEPATITIS C VIRUS GENOME RNA", JOURNAL OF VIROLOGY, THE AMERICAN SOCIETY FOR MICROBIOLOGY, US, vol. 70, no. 6, June 1996 (1996-06-01), pages 3363 - 3371, XP000985963, ISSN: 0022-538X *
S. REIGADAS ET AL: "HCV RNA-dependent RNA polymerase replicates in vitro the 3' terminal region of the minus-strand viral RNA more efficiently than the 3' terminal region of the plus RNA", EUROPEAN JOURNAL OF BIOCHEMISTRY, vol. 268, February 2001 (2001-02-01), pages 5857 - 5867, XP002194352 *
TANAKA T ET AL: "STRUCTURE OF THE 3' TERMINUS OF THE HEPATITIS C VIRUS GENOME", JOURNAL OF VIROLOGY, THE AMERICAN SOCIETY FOR MICROBIOLOGY, US, vol. 70, no. 5, May 1996 (1996-05-01), pages 3307 - 3312, XP000985964, ISSN: 0022-538X *
W. ZHONG ET AL: "De Novo initiation of RNA synthesis by hepatitis C Virus nonstructural protein 5B Polymerase", JOURNAL OF VIROLOGY., vol. 74, no. 4, February 2000 (2000-02-01), THE AMERICAN SOCIETY FOR MICROBIOLOGY., US, pages 2017 - 2022, XP002194346, ISSN: 0022-538X *
XIN-LAN SUN ET AL: "De Novo RNA Synthesis catalyzed by HCV RNA-dependent RNA Polymerase", BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS., vol. 268, February 2000 (2000-02-01), ACADEMIC PRESS INC. ORLANDO, FL., US, pages 798 - 803, XP002194347, ISSN: 0006-291X *
YAMADA N ET AL: "SHORT COMMUNICATION GENETIC ORGANIZATION AND DIVERSITY OF THE 3' NONCODING REGION OF THE HEPATITIS C VIRUS GENOME", VIROLOGY, ACADEMIC PRESS,ORLANDO, US, vol. 223, 1996, pages 255 - 261, XP000929299, ISSN: 0042-6822 *

Also Published As

Publication number Publication date
WO2001083736A2 (en) 2001-11-08
US20010055756A1 (en) 2001-12-27
EP1278837A2 (en) 2003-01-29
AU2001254563A1 (en) 2001-11-12

Similar Documents

Publication Publication Date Title
Corda et al. Spectrum of DNA-platinum adduct recognition by prokaryotic and eukaryotic DNA-dependent RNA polymerases
AU2003234196A1 (en) Functionalized nanoparticles and methods of use
Bakin et al. The single pseudouridine residue in Escherichia coli 16S RNA is located at position 516
EP1667168A4 (en) Composition for polymer solid electrolyte, polymer solid electrolyte, polymer, polymer solid electrolyte battery, ion-conductive membrane, copolymer and process for producing the copolymer
Richardson et al. Characterization of the bacteriophage T4 gene 41 DNA helicase
EP2484687A3 (en) Methods and compositions for seamless cloning of nucleic acid molecules
ATE373671T1 (en) AMINOOXY-MODIFIED OLIGONUCLEOTIDES
WO2003023015A3 (en) Method for expression of small antiviral rna molecules within a cell
WO2003039443A3 (en) Novel genetic markers for leukemias
GB2395953A (en) Labelled nucleotides
CA2327547A1 (en) Oligonucleotides containing pyrazolo[3,4-d]pyrimidines for hybridization and mismatch discrimination
WO2002061133A3 (en) Nucleic acid detection using structured probes
IL145497A0 (en) L-ribo-lna analogues
WO2003087301A8 (en) Methods and compositions for dna manipulation
WO2002034951A3 (en) Compositions and methods for detecting human immunodeficiency virus 2 (hiv-2)
JP2010532979A5 (en)
Brulé et al. Structural and functional properties of the HIV-1 RNA-tRNA (Lys) 3 primer complex annealed by the nucleocapsid protein: comparison with the heat-annealed complex.
WO2001083736A3 (en) Internal de novo initiation sites of the hcv ns5b polymerase and use thereof
EA200401207A1 (en) METHOD OF DETECTION AND DETERMINATION OF THE TYPE OF HUMAN PAPILLOMAVIRUS USING AMPLIFICATION-HYBRIDIZATION
WO2003104470A3 (en) Retrons for gene targeting
EP2383349A3 (en) Primer and probe for detection of mycobacterium avium and method for detection of mycobacterium avium using the same
Vidalin et al. In vitro inhibition of hepatitis C virus gene expression by chemically modified antisense oligodeoxynucleotides
EP1634962A4 (en) Method of detecting target nucleotide sequence, detection target structure to be used in embodying the method, process for producing the same and assay kit for detecting target nucleotide sequence
MXPA05006015A (en) TREATMENT OF HSV-RELATED PATHOLOGIES USING ssDNA.
WO2003027290A1 (en) Method of imparting or controlling fertility with the use of fertility restoring gene for rice bt-male sterility cytoplasm and method of judging the existence of fertility restoring gene

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CR CU CZ DE DK DM DZ EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
AK Designated states

Kind code of ref document: A3

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CR CU CZ DE DK DM DZ EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A3

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

WWE Wipo information: entry into national phase

Ref document number: 2001927534

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 2001927534

Country of ref document: EP

WWW Wipo information: withdrawn in national office

Ref document number: 2001927534

Country of ref document: EP

NENP Non-entry into the national phase

Ref country code: JP