WO2011133584A3 - Nucleic acid compounds for inhibiting hras gene expression and uses thereof - Google Patents

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

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Publication number
WO2011133584A3
WO2011133584A3 PCT/US2011/033102 US2011033102W WO2011133584A3 WO 2011133584 A3 WO2011133584 A3 WO 2011133584A3 US 2011033102 W US2011033102 W US 2011033102W WO 2011133584 A3 WO2011133584 A3 WO 2011133584A3
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WIPO (PCT)
Prior art keywords
nucleic acid
hras
strand
gene expression
complexes
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Application number
PCT/US2011/033102
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French (fr)
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WO2011133584A8 (en
WO2011133584A2 (en
Inventor
Narendra K. Vaish
Shaguna Seth
Kathy L. Fosnaugh
Michael E. Houston
Michael V. Templin
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Marina Biotech, Inc.
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Publication date
Application filed by Marina Biotech, Inc. filed Critical Marina Biotech, Inc.
Publication of WO2011133584A2 publication Critical patent/WO2011133584A2/en
Publication of WO2011133584A3 publication Critical patent/WO2011133584A3/en
Publication of WO2011133584A8 publication Critical patent/WO2011133584A8/en

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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
    • C12N15/113—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
    • C12N15/1135—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 against oncogenes or tumor suppressor genes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/344—Position-specific modifications, e.g. on every purine, at the 3'-end

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Biomedical Technology (AREA)
  • Organic Chemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Zoology (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biotechnology (AREA)
  • Oncology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Plant Pathology (AREA)
  • Veterinary Medicine (AREA)
  • Microbiology (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Biochemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

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 HRAS 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 HRAS gene in a cell or in a subject to treat a HRAS-related disease.
PCT/US2011/033102 2010-04-19 2011-04-19 Nucleic acid compounds for inhibiting hras gene expression and uses thereof WO2011133584A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US32575710P 2010-04-19 2010-04-19
US61/325,757 2010-04-19

Publications (3)

Publication Number Publication Date
WO2011133584A2 WO2011133584A2 (en) 2011-10-27
WO2011133584A3 true WO2011133584A3 (en) 2012-01-12
WO2011133584A8 WO2011133584A8 (en) 2012-06-07

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Family Applications (1)

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PCT/US2011/033102 WO2011133584A2 (en) 2010-04-19 2011-04-19 Nucleic acid compounds for inhibiting hras gene expression and uses thereof

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Families Citing this family (6)

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CN106460025A (en) 2014-03-25 2017-02-22 阿克丘勒斯治疗公司 UNA oligomers having reduced off-target effects in gene silencing
US9856475B2 (en) 2014-03-25 2018-01-02 Arcturus Therapeutics, Inc. Formulations for treating amyloidosis
WO2015148582A1 (en) * 2014-03-25 2015-10-01 Arcturus Therapeutics, Inc. Transthyretin allele selective una oligomers for gene silencing
US10519447B2 (en) 2015-04-01 2019-12-31 Arcturus Therapeutics, Inc. Therapeutic UNA oligomers and uses thereof
WO2017015671A1 (en) 2015-07-23 2017-01-26 Arcturus Therapeutics, Inc. Compositions for treating amyloidosis
IL260690A (en) * 2018-07-19 2018-12-31 Yeda Res & Dev Sphingosine analogs and use thereof against bacterial lung infections

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