WO2005078094A3 - Stabilized rnas as transfection controls and silencing reagents - Google Patents

Stabilized rnas as transfection controls and silencing reagents Download PDF

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Publication number
WO2005078094A3
WO2005078094A3 PCT/US2005/003365 US2005003365W WO2005078094A3 WO 2005078094 A3 WO2005078094 A3 WO 2005078094A3 US 2005003365 W US2005003365 W US 2005003365W WO 2005078094 A3 WO2005078094 A3 WO 2005078094A3
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WO
WIPO (PCT)
Prior art keywords
terminal
nucleotide
alkyl
molecules
antisense nucleotide
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/US2005/003365
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French (fr)
Other versions
WO2005078094A2 (en
Inventor
Devin Leake
Anastasia Khvorova
Yuriy Fedorov
Michael O Delaney
Barbara Robertson
Emily Anderson
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Dharmacon Inc
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Dharmacon Inc
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Filing date
Publication date
Application filed by Dharmacon Inc filed Critical Dharmacon Inc
Priority to AT05712710T priority Critical patent/ATE447024T1/en
Priority to EP05712710A priority patent/EP1718747B1/en
Priority to DE602005017362T priority patent/DE602005017362D1/en
Publication of WO2005078094A2 publication Critical patent/WO2005078094A2/en
Publication of WO2005078094A3 publication Critical patent/WO2005078094A3/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
    • C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/111—General methods applicable to biologically active non-coding nucleic acids
    • 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
    • C12N15/113—Non-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
    • 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
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/10—Type of nucleic acid
    • C12N2310/14—Type of nucleic acid interfering nucleic acids [NA]
    • 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
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/321—2'-O-R Modification
    • 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
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/322—2'-R Modification
    • 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
    • C12N2320/00—Applications; Uses
    • C12N2320/50—Methods for regulating/modulating their activity
    • C12N2320/51—Methods for regulating/modulating their activity modulating the chemical stability, e.g. nuclease-resistance

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Saccharide Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

RNA molecules, including siRNA molecules and related control, trackability and exaequo agents with specific stability modifications are provided. These molecules are particularly advantageous as transfection control reagents. The molecules include first and second 5' terminal sense nucleotides with 2'-O-alkyl groups and a label on the ferst 5' terminal sense nucleotide, in conjunction with at least one additional 2'-O-alkyl pyrimidine modified sense nucleotide, and either: (i) at least one 2' fluoro modified pyrimidine antisense nucleotide and a phosphorylated first 5' terminal antisense nucleotide; or (ii) a first and second 5' terminal antisense nucleotide with 2'-O-alkyl modifications and at least one additional 2'-O-alkyl pyrimidine modified antisense nucleotide.
PCT/US2005/003365 2004-02-06 2005-02-04 Stabilized rnas as transfection controls and silencing reagents Ceased WO2005078094A2 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
AT05712710T ATE447024T1 (en) 2004-02-06 2005-02-04 STABILIZED RNAS AS TRANSFECTION CONTROLS AND SILENCING REAGENTS
EP05712710A EP1718747B1 (en) 2004-02-06 2005-02-04 Stabilized rnas as transfection controls and silencing reagents
DE602005017362T DE602005017362D1 (en) 2004-02-06 2005-02-04 STABILIZED RNAS AS TRANSFECTION CONTROLS AND SILENCING REAGENTS

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US54264604P 2004-02-06 2004-02-06
US60/542,646 2004-02-06
US54364004P 2004-02-10 2004-02-10
US60/543,640 2004-02-10
US57227004P 2004-05-18 2004-05-18
US60/572,270 2004-05-18

Publications (2)

Publication Number Publication Date
WO2005078094A2 WO2005078094A2 (en) 2005-08-25
WO2005078094A3 true WO2005078094A3 (en) 2006-03-23

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2005/003365 Ceased WO2005078094A2 (en) 2004-02-06 2005-02-04 Stabilized rnas as transfection controls and silencing reagents

Country Status (5)

Country Link
US (1) US20070269889A1 (en)
EP (2) EP2123759B1 (en)
AT (1) ATE447024T1 (en)
DE (1) DE602005017362D1 (en)
WO (1) WO2005078094A2 (en)

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US7595387B2 (en) 2004-04-01 2009-09-29 Dharmacon, Inc. Modified polynucleotides for reducing off-target effects in RNA interference
US8188060B2 (en) 2008-02-11 2012-05-29 Dharmacon, Inc. Duplex oligonucleotides with enhanced functionality in gene regulation
US8252755B2 (en) 2006-09-22 2012-08-28 Dharmacon, Inc. Duplex oligonucleotide complexes and methods for gene silencing by RNA interference

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