WO2011139842A3 - Nucleic acid compounds for inhibiting fgfr3 gene expression and uses thereof - Google Patents

Nucleic acid compounds for inhibiting fgfr3 gene expression and uses thereof Download PDF

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Publication number
WO2011139842A3
WO2011139842A3 PCT/US2011/034352 US2011034352W WO2011139842A3 WO 2011139842 A3 WO2011139842 A3 WO 2011139842A3 US 2011034352 W US2011034352 W US 2011034352W WO 2011139842 A3 WO2011139842 A3 WO 2011139842A3
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WO
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Prior art keywords
nucleic acid
end
strand
fgfr3
gene expression
Prior art date
Application number
PCT/US2011/034352
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French (fr)
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WO2011139842A2 (en )
Inventor
Kathy L. Fosnaugh
Michael E. Houston
Shaguna Seth
Michael V. Templin
Narendra K. Vaish
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Marina Biotech, Inc.
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    • 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
    • C12N15/1138Non-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 receptors or cell surface proteins
    • 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
    • C12N2310/14Type of nucleic acid interfering N.A.
    • 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
    • C12N2310/30Chemical structure
    • C12N2310/32Chemical structure of the sugar
    • C12N2310/3212'-O-R Modification
    • 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
    • C12N2310/30Chemical structure
    • C12N2310/32Chemical structure of the sugar
    • C12N2310/323Chemical structure of the sugar modified ring structure
    • 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
    • C12N2310/533Physical structure partially self-complementary or closed having a mismatch or nick in at least one of the strands

Abstract

This disclosure provides double- stranded nucleic acid complexes having one or more hydroxymethyl substituted nucleomonomer(s) and wherein one strand is complementary to a FGFR3 mRNA. Nucleic acid complexes of the disclosure may be useful for therapeutic applications, diagnostic applications or research applications. Nucleic complexes include short interfering RNA complexes (siRNA) capable of modulating gene expression comprising an antisense strand and a continuous or a discontinuous passenger strand ("sense strand"). Further, one or more hydroxymethyl substituted nucleomonomer(s) of this disclosure may be positioned at the 3 '-end, at the 5 '-end, at both the 3 '-end and 5 'end, and/or in a double- stranded region of a nucleic acid complex. Also provided are methods of decreasing expression of a FGFR3 gene in a cell or in a subject to treat a FGFR3-related disease.
PCT/US2011/034352 2010-04-28 2011-04-28 Nucleic acid compounds for inhibiting fgfr3 gene expression and uses thereof WO2011139842A3 (en)

Priority Applications (2)

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US32903410 true 2010-04-28 2010-04-28
US61/329,034 2010-04-28

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WO2011139842A2 true WO2011139842A2 (en) 2011-11-10
WO2011139842A3 true true WO2011139842A3 (en) 2012-01-26

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PCT/US2011/034354 WO2011139843A3 (en) 2010-04-28 2011-04-28 Multi-sirna compositions for reducing gene expression

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Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013088191A1 (en) 2011-12-12 2013-06-20 Institut National De La Sante Et De La Recherche Medicale (Inserm) Antagonist of the fibroblast growth factor receptor 3 (fgfr3) for use in the treatment or the prevention of skeletal disorders linked with abnormal activation of fgfr3
US9725723B2 (en) 2012-11-26 2017-08-08 Roche Innovation Center Copenhagen A/S Compositions and methods for modulation of FGFR3 expression
WO2016139227A1 (en) 2015-03-03 2016-09-09 INSERM (Institut National de la Santé et de la Recherche Médicale) Fgfr3 antagonists
CA3005937A1 (en) * 2015-12-13 2017-06-22 Nitto Denko Corporation Sirna structures for high activity and reduced off target

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WO2011139843A2 (en) 2011-11-10 application
WO2011139842A2 (en) 2011-11-10 application
WO2011139843A3 (en) 2012-01-26 application

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