WO2004044139A3 - Modified oligonucleotides for use in rna interference - Google Patents

Modified oligonucleotides for use in rna interference Download PDF

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Publication number
WO2004044139A3
WO2004044139A3 PCT/US2003/035086 US0335086W WO2004044139A3 WO 2004044139 A3 WO2004044139 A3 WO 2004044139A3 US 0335086 W US0335086 W US 0335086W WO 2004044139 A3 WO2004044139 A3 WO 2004044139A3
Authority
WO
WIPO (PCT)
Prior art keywords
modified oligonucleotides
rna interference
rna
nucleoside
hydroxyl
Prior art date
Application number
PCT/US2003/035086
Other languages
French (fr)
Other versions
WO2004044139A2 (en
Inventor
Brenda F Baker
Anne B Eldrup
Muthiah Manoharan
Balkrishen Bhat
Richard Griffey
Eric E Swayze
Original Assignee
Isis Parmaceuticals Inc
Brenda F Baker
Anne B Eldrup
Muthiah Manoharan
Balkrishen Bhat
Richard Griffey
Eric E Swayze
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 Isis Parmaceuticals Inc, Brenda F Baker, Anne B Eldrup, Muthiah Manoharan, Balkrishen Bhat, Richard Griffey, Eric E Swayze filed Critical Isis Parmaceuticals Inc
Priority to AU2003295387A priority Critical patent/AU2003295387A1/en
Publication of WO2004044139A2 publication Critical patent/WO2004044139A2/en
Publication of WO2004044139A3 publication Critical patent/WO2004044139A3/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • C07H21/04—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with deoxyribosyl as saccharide radical
    • 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
    • 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 N.A.
    • 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
    • C12N2310/00—Structure or type of the nucleic acid
    • C12N2310/30—Chemical structure
    • C12N2310/32—Chemical structure of the sugar
    • C12N2310/323—Chemical structure of the sugar modified ring structure
    • 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
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/343—Spatial arrangement of the modifications having patterns, e.g. ==--==--==--
    • 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
    • C12N2310/35—Nature of the modification
    • C12N2310/352—Nature of the modification linked to the nucleic acid via a carbon atom
    • C12N2310/3521—Methyl
    • 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
    • C12N2310/35—Nature of the modification
    • C12N2310/353—Nature of the modification linked to the nucleic acid via an atom other than carbon
    • C12N2310/3533—Halogen
    • 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

Abstract

The present invention provides modified oligonucleotides for use in the RNA interference pathway of gene modulation. At least one nucleoside has a 2'-modification other than hydroxyl that gives an RNA like 3'-endo sugar conformation. The modified oligonucleotides are also provided having a 5'-phosphate group.
PCT/US2003/035086 2002-11-05 2003-11-04 Modified oligonucleotides for use in rna interference WO2004044139A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU2003295387A AU2003295387A1 (en) 2002-11-05 2003-11-04 Modified oligonucleotides for use in rna interference

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US42376002P 2002-11-05 2002-11-05
US60/423,760 2002-11-05

Publications (2)

Publication Number Publication Date
WO2004044139A2 WO2004044139A2 (en) 2004-05-27
WO2004044139A3 true WO2004044139A3 (en) 2005-02-10

Family

ID=32312707

Family Applications (6)

Application Number Title Priority Date Filing Date
PCT/US2003/035063 WO2004044132A2 (en) 2002-11-05 2003-11-04 Modified oligonucleotides for use in rna interference
PCT/US2003/035086 WO2004044139A2 (en) 2002-11-05 2003-11-04 Modified oligonucleotides for use in rna interference
PCT/US2003/035061 WO2004043979A2 (en) 2002-11-05 2003-11-04 Sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation
PCT/US2003/035064 WO2004044133A2 (en) 2002-11-05 2003-11-04 Modified oligonucleotides for use in rna interference
PCT/US2003/035071 WO2004044136A2 (en) 2002-11-05 2003-11-04 Compositions comprising alternating 2’-modified nucleosides for use in gene modulation
PCT/US2003/035146 WO2004042029A2 (en) 2002-11-05 2003-11-04 Oligomers comprising modified bases for binding cytosine and uracil or thymine and their use

Family Applications Before (1)

Application Number Title Priority Date Filing Date
PCT/US2003/035063 WO2004044132A2 (en) 2002-11-05 2003-11-04 Modified oligonucleotides for use in rna interference

Family Applications After (4)

Application Number Title Priority Date Filing Date
PCT/US2003/035061 WO2004043979A2 (en) 2002-11-05 2003-11-04 Sugar surrogate-containing oligomeric compounds and compositions for use in gene modulation
PCT/US2003/035064 WO2004044133A2 (en) 2002-11-05 2003-11-04 Modified oligonucleotides for use in rna interference
PCT/US2003/035071 WO2004044136A2 (en) 2002-11-05 2003-11-04 Compositions comprising alternating 2’-modified nucleosides for use in gene modulation
PCT/US2003/035146 WO2004042029A2 (en) 2002-11-05 2003-11-04 Oligomers comprising modified bases for binding cytosine and uracil or thymine and their use

Country Status (5)

Country Link
US (3) US8604183B2 (en)
EP (3) EP1578765A4 (en)
AU (6) AU2003287502B2 (en)
CA (2) CA2504929C (en)
WO (6) WO2004044132A2 (en)

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