WO1996018732A3 - Sequence-specific inhibition of dna synthesis by triplex-forming oligonucleotides - Google Patents

Sequence-specific inhibition of dna synthesis by triplex-forming oligonucleotides Download PDF

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Publication number
WO1996018732A3
WO1996018732A3 PCT/US1995/016368 US9516368W WO9618732A3 WO 1996018732 A3 WO1996018732 A3 WO 1996018732A3 US 9516368 W US9516368 W US 9516368W WO 9618732 A3 WO9618732 A3 WO 9618732A3
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WO
WIPO (PCT)
Prior art keywords
sequence
dna
replication
dna synthesis
triplex
Prior art date
Application number
PCT/US1995/016368
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French (fr)
Other versions
WO1996018732A9 (en
WO1996018732A2 (en
Inventor
Sergei M Mirkin
G M Samadashwily
Original Assignee
Univ Pennsylvania
Sergei M Mirkin
G M Samadashwily
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.)
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Publication date
Application filed by Univ Pennsylvania, Sergei M Mirkin, G M Samadashwily filed Critical Univ Pennsylvania
Publication of WO1996018732A2 publication Critical patent/WO1996018732A2/en
Publication of WO1996018732A9 publication Critical patent/WO1996018732A9/en
Publication of WO1996018732A3 publication Critical patent/WO1996018732A3/en

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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088Compounds having three or more nucleosides or nucleotides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088Compounds having three or more nucleosides or nucleotides
    • A61K31/711Natural deoxyribonucleic acids, i.e. containing only 2'-deoxyriboses attached to adenine, guanine, cytosine or thymine and having 3'-5' phosphodiester links
    • 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
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • 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
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C12N15/1131Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against 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
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C12N15/1131Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against viruses
    • C12N15/1133Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against viruses against herpetoviridae, e.g. HSV
    • 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
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C12N15/1135Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against oncogenes or tumor suppressor genes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • 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
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/10Type of nucleic acid
    • C12N2310/15Nucleic acids forming more than 2 strands, e.g. TFOs
    • C12N2310/152Nucleic acids forming more than 2 strands, e.g. TFOs on a single-stranded target, e.g. fold-back TFOs
    • 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
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/50Physical structure
    • C12N2310/53Physical structure partially self-complementary or closed
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02ATECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Zoology (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Organic Chemistry (AREA)
  • Wood Science & Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Physics & Mathematics (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Biophysics (AREA)
  • Virology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Oncology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

Specifically designed oligodeoxyribonucleotides form triplexes in single- or double-strand DNA at homopurine-homopyrimidine targets. These triplexes block in vitro DNA synthesis by all DNA polymerases studied, including Sequenase®, Taq, Vent, and Pol I. A similar phenomenon occurs when DNA polymerases are supplemented with accessory replication proteins, including SSB protein. Replication blockage is highly sequence-specific and even one or two point substitutions within either the target sequence or the oligonucleotide abolish the effect. Sequence-specific blocking of DNA replication in vivo is facilitated by the methods and compositions of the present invention.
PCT/US1995/016368 1994-12-15 1995-12-14 Sequence-specific inhibition of dna synthesis by triplex-forming oligonucleotides WO1996018732A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US35808994A 1994-12-15 1994-12-15
US08/358,089 1994-12-15

Publications (3)

Publication Number Publication Date
WO1996018732A2 WO1996018732A2 (en) 1996-06-20
WO1996018732A9 WO1996018732A9 (en) 1996-10-03
WO1996018732A3 true WO1996018732A3 (en) 1997-02-13

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1995/016368 WO1996018732A2 (en) 1994-12-15 1995-12-14 Sequence-specific inhibition of dna synthesis by triplex-forming oligonucleotides

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WO (1) WO1996018732A2 (en)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6914137B2 (en) 1997-12-06 2005-07-05 Dna Research Innovations Limited Isolation of nucleic acids
JP4220744B2 (en) 2001-09-25 2009-02-04 株式会社アイシン・コスモス研究所 Processing libraries using ligation inhibition
US20060135455A1 (en) 2004-06-01 2006-06-22 Reza Sheikhnejad Methods and compositions for the inhibition of gene expression
US7807647B2 (en) 2004-06-01 2010-10-05 Pronai Therapeutics, Inc. Methods and compositions for cancer therapy
US8815599B2 (en) 2004-06-01 2014-08-26 Pronai Therapeutics, Inc. Methods and compositions for the inhibition of gene expression
CA2631677C (en) 2005-12-01 2014-08-12 Pronai Therapeutics, Inc. Amphoteric liposome formulation
WO2023187394A1 (en) * 2022-03-31 2023-10-05 The University Court Of The University Of Edinburgh Controllable gene expression

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993007295A1 (en) * 1991-10-07 1993-04-15 The Johns Hopkins University Formation of triple helix complexes of single stranded nucleic acids using nucleoside oligomers
WO1994017086A1 (en) * 1993-01-25 1994-08-04 Apollon, Inc. Gene regulation by targeting putative intramolecular triple helix

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1993007295A1 (en) * 1991-10-07 1993-04-15 The Johns Hopkins University Formation of triple helix complexes of single stranded nucleic acids using nucleoside oligomers
WO1994017086A1 (en) * 1993-01-25 1994-08-04 Apollon, Inc. Gene regulation by targeting putative intramolecular triple helix

Non-Patent Citations (7)

* Cited by examiner, † Cited by third party
Title
CONFERENCE ON PHARMACEUTICAL DESIGN II: NUCLEIC ACID BINDING DRUGS; HELD FROM 31-01 TO 01-02-94 IN PALO ALTO, CA, USA *
DAYN, A. ET AL.: "Intramolecular DNA triplexes: unusual sequence requirements and influence on DNA polymerization", PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA, vol. 89, December 1992 (1992-12-01), WASHINGTON US, pages 11406 - 11410, XP002007117 *
GIOVANNANGELI, C. ET AL.: "Oligonucleotide clamps arrest DNA synthesis on a single-stranded DNA target", PNAS 90 (01-11-93);10013-7, XP002007115 *
MIRKIN, S. & FRANK-KAMENETSKII, M.: "H-DNA and related structures", ANNU.REV.BIOPHYS.BIOMOL.STRUCT., vol. 23, 1994, pages 541 - 576, XP000574782 *
SAMADASHWILY, G. & MIRKIN, S.: "Trapping DNA polymerases using triplex-forming oligodeoxyribonucleotides", GENE 149 (4-11-94);127-36, XP002007113 *
SAMADASHWILY, G. ET AL.: "Suicidal nucleotide sequences for DNA polymerization", EMBO JOURNAL, vol. 12, 1993, EYNSHAM, OXFORD GB, pages 4975 - 4983, XP002007114 *
VO, T. ET AL.: "Targeting pyrimidine single strands by triplex formation: structural optimization of binding", NAR 23 (11-08-95);2937-44, XP002007116 *

Also Published As

Publication number Publication date
WO1996018732A2 (en) 1996-06-20

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