WO2008109498A8 - Nucleic acid compounds for inhibiting hdac gene expression and uses thereof - Google Patents
Nucleic acid compounds for inhibiting hdac gene expression and uses thereof Download PDFInfo
- Publication number
- WO2008109498A8 WO2008109498A8 PCT/US2008/055612 US2008055612W WO2008109498A8 WO 2008109498 A8 WO2008109498 A8 WO 2008109498A8 US 2008055612 W US2008055612 W US 2008055612W WO 2008109498 A8 WO2008109498 A8 WO 2008109498A8
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- hdac
- nucleic acid
- gene expression
- acid compounds
- mdrna
- Prior art date
Links
- 230000014509 gene expression Effects 0.000 title abstract 3
- 108020004707 nucleic acids Proteins 0.000 title abstract 2
- 102000039446 nucleic acids Human genes 0.000 title abstract 2
- -1 Nucleic acid compounds Chemical class 0.000 title 1
- 230000002401 inhibitory effect Effects 0.000 title 1
- 108090000353 Histone deacetylase Proteins 0.000 abstract 3
- 108091005772 HDAC11 Proteins 0.000 abstract 2
- 102000003964 Histone deacetylase Human genes 0.000 abstract 2
- 102100039996 Histone deacetylase 1 Human genes 0.000 abstract 2
- 102100039385 Histone deacetylase 11 Human genes 0.000 abstract 2
- 102100039999 Histone deacetylase 2 Human genes 0.000 abstract 2
- 102100021455 Histone deacetylase 3 Human genes 0.000 abstract 2
- 102100021454 Histone deacetylase 4 Human genes 0.000 abstract 2
- 102100021453 Histone deacetylase 5 Human genes 0.000 abstract 2
- 102100022537 Histone deacetylase 6 Human genes 0.000 abstract 2
- 102100038719 Histone deacetylase 7 Human genes 0.000 abstract 2
- 102100038715 Histone deacetylase 8 Human genes 0.000 abstract 2
- 102100038720 Histone deacetylase 9 Human genes 0.000 abstract 2
- 101001035024 Homo sapiens Histone deacetylase 1 Proteins 0.000 abstract 2
- 101001035011 Homo sapiens Histone deacetylase 2 Proteins 0.000 abstract 2
- 101000899282 Homo sapiens Histone deacetylase 3 Proteins 0.000 abstract 2
- 101000899259 Homo sapiens Histone deacetylase 4 Proteins 0.000 abstract 2
- 101000899255 Homo sapiens Histone deacetylase 5 Proteins 0.000 abstract 2
- 101000899330 Homo sapiens Histone deacetylase 6 Proteins 0.000 abstract 2
- 101001032113 Homo sapiens Histone deacetylase 7 Proteins 0.000 abstract 2
- 101001032118 Homo sapiens Histone deacetylase 8 Proteins 0.000 abstract 2
- 101001032092 Homo sapiens Histone deacetylase 9 Proteins 0.000 abstract 2
- 101001035694 Homo sapiens Polyamine deacetylase HDAC10 Proteins 0.000 abstract 2
- WWGBHDIHIVGYLZ-UHFFFAOYSA-N N-[4-[3-[[[7-(hydroxyamino)-7-oxoheptyl]amino]-oxomethyl]-5-isoxazolyl]phenyl]carbamic acid tert-butyl ester Chemical compound C1=CC(NC(=O)OC(C)(C)C)=CC=C1C1=CC(C(=O)NCCCCCCC(=O)NO)=NO1 WWGBHDIHIVGYLZ-UHFFFAOYSA-N 0.000 abstract 2
- 102100039388 Polyamine deacetylase HDAC10 Human genes 0.000 abstract 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical group O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 abstract 2
- 230000003247 decreasing effect Effects 0.000 abstract 2
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 abstract 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 abstract 1
- 230000000295 complement effect Effects 0.000 abstract 1
- 201000010099 disease Diseases 0.000 abstract 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
- 230000030279 gene silencing Effects 0.000 abstract 1
- 108020004999 messenger RNA Proteins 0.000 abstract 1
- 238000000034 method Methods 0.000 abstract 1
- 238000012986 modification Methods 0.000 abstract 1
- 230000004048 modification Effects 0.000 abstract 1
- 150000007523 nucleic acids Chemical class 0.000 abstract 1
- 239000002777 nucleoside Substances 0.000 abstract 1
- 150000003833 nucleoside derivatives Chemical class 0.000 abstract 1
- DWRXFEITVBNRMK-JXOAFFINSA-N ribothymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 DWRXFEITVBNRMK-JXOAFFINSA-N 0.000 abstract 1
- 229920002477 rna polymer Polymers 0.000 abstract 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 abstract 1
- 229940045145 uridine Drugs 0.000 abstract 1
Classifications
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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
- C12N15/1137—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 enzymes
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
- C12N2310/11—Antisense
- C12N2310/111—Antisense spanning the whole gene, or a large part of it
-
- 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]
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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
- 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
- C12N2310/323—Chemical structure of the sugar modified ring structure
- C12N2310/3231—Chemical structure of the sugar modified ring structure having an additional ring, e.g. LNA, ENA
-
- 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
- C12N2310/33—Chemical structure of the base
-
- 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
- C12N2310/50—Physical structure
- C12N2310/53—Physical structure partially self-complementary or closed
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Genetics & Genomics (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Wood Science & Technology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Zoology (AREA)
- Biotechnology (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- Rheumatology (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Virology (AREA)
- Pain & Pain Management (AREA)
- Biochemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present disclosure provides meroduplex ribonucleic acid molecules (mdRNA) capable of decreasing or silencing HDAC (e.g., HDAC1, HDAC2, HDAC3, HDAC4, HDAC5, HDAC6, HDAC7A, HDAC8, HDAC9, HDAC10, HDAC11) gene expression. An mdRNA of this disclosure comprises at least three strands that combine to form at least two non-overlapping double-stranded regions separated by a nick or gap wherein one strand is complementary to an HDAC1, HDAC2, HDAC3, HDAC4, HDAC5, HDAC6, HDAC7A, HDAC8, HDAC9, HDAC10, or HDAC11 1 mRNA. In addition, the meroduplex may have at least one uridine substituted with a 5-methyluridine, a nucleoside replaced with a locked nucleic acid, or optionally other modifications, and any combination thereof. Also provided are methods of decreasing expression of an HDAC gene in a cell or in a subject to treat an HDAC-related disease.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US12/552,082 US20100105134A1 (en) | 2007-03-02 | 2009-09-01 | Nucleic acid compounds for inhibiting gene expression and uses thereof |
| US13/327,545 US20130011922A1 (en) | 2007-03-02 | 2011-12-15 | Nucleic acid compounds for inhibiting gene expression and uses thereof |
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US93494007P | 2007-03-02 | 2007-03-02 | |
| US60/934,940 | 2007-03-02 | ||
| US93493007P | 2007-03-16 | 2007-03-16 | |
| US60/934,930 | 2007-03-16 | ||
| US1240407P | 2007-12-07 | 2007-12-07 | |
| US61/012,404 | 2007-12-07 |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US2008/055622 Continuation-In-Part WO2008109503A1 (en) | 2007-03-02 | 2008-03-03 | Nucleic acid compounds for inhibiting ms4a1 gene expression and uses thereof |
Related Child Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US2008/055563 Continuation-In-Part WO2008109475A1 (en) | 2007-03-02 | 2008-02-29 | Nucleic acid compounds for inhibiting sirt2 gene expression and uses thereof |
| US12/552,082 Continuation-In-Part US20100105134A1 (en) | 2007-03-02 | 2009-09-01 | Nucleic acid compounds for inhibiting gene expression and uses thereof |
| AU2009212920A Division AU2009212920A1 (en) | 2007-03-02 | 2009-09-01 | Nucleic acid compounds for inhibiting gene expression and uses thereof |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| WO2008109498A2 WO2008109498A2 (en) | 2008-09-12 |
| WO2008109498A3 WO2008109498A3 (en) | 2009-03-12 |
| WO2008109498A4 WO2008109498A4 (en) | 2009-04-30 |
| WO2008109498A8 true WO2008109498A8 (en) | 2009-12-10 |
Family
ID=39720233
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US2008/055612 WO2008109498A2 (en) | 2007-03-02 | 2008-03-03 | Nucleic acid compounds for inhibiting hdac gene expression and uses thereof |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2008109498A2 (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9074205B2 (en) | 2006-10-18 | 2015-07-07 | Marina Biotech, Inc. | Nicked or gapped nucleic acid molecules and uses thereof |
| WO2010056677A1 (en) * | 2008-11-12 | 2010-05-20 | Duke University | Methods of inhibiting cancer cell growth with hdac inhibitors and methods of screening for hdac10 inhibitors |
| EP3099811B1 (en) * | 2014-01-28 | 2018-09-12 | Qiagen GmbH | Method of amplification of a short tandem repeat locus |
| CN111840311B (en) * | 2020-07-31 | 2021-11-12 | 上海交通大学医学院附属第九人民医院 | Use of siRNA molecule composition for preparing medicament for inhibiting scar formation against HDAC5 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060148743A1 (en) * | 2001-05-18 | 2006-07-06 | Vasant Jadhav | RNA interference mediated inhibition of histone deacetylase (HDAC) gene expression using short interfering nucleic acid (siNA) |
| WO2008030239A1 (en) * | 2006-09-05 | 2008-03-13 | Sirna Therapeutics, Inc. | RNA INTERFERENCE MEDIATED INHIBITION OF HISTONE DEACETYLASE (HDAC) GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA) |
| US20050136437A1 (en) * | 2003-08-25 | 2005-06-23 | Nastech Pharmaceutical Company Inc. | Nanoparticles for delivery of nucleic acids and stable double-stranded RNA |
| KR20080066987A (en) * | 2005-11-04 | 2008-07-17 | 나스텍 파마수티컬 컴퍼니 인코포레이티드 | Peptide-Dicer Substrates RNA Conjugates as Delivery Carriers for SiRNA |
| EP2002004B1 (en) * | 2006-03-23 | 2015-10-14 | Roche Innovation Center Copenhagen A/S | Small internally segmented interfering rna |
| US9074205B2 (en) * | 2006-10-18 | 2015-07-07 | Marina Biotech, Inc. | Nicked or gapped nucleic acid molecules and uses thereof |
-
2008
- 2008-03-03 WO PCT/US2008/055612 patent/WO2008109498A2/en active Application Filing
Also Published As
| Publication number | Publication date |
|---|---|
| WO2008109498A2 (en) | 2008-09-12 |
| WO2008109498A4 (en) | 2009-04-30 |
| WO2008109498A3 (en) | 2009-03-12 |
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