WO2009078470A1 - 多糖/2本鎖rna複合体 - Google Patents

多糖/2本鎖rna複合体 Download PDF

Info

Publication number
WO2009078470A1
WO2009078470A1 PCT/JP2008/073125 JP2008073125W WO2009078470A1 WO 2009078470 A1 WO2009078470 A1 WO 2009078470A1 JP 2008073125 W JP2008073125 W JP 2008073125W WO 2009078470 A1 WO2009078470 A1 WO 2009078470A1
Authority
WO
WIPO (PCT)
Prior art keywords
double
complex
stranded rna
stranded
polysaccharide
Prior art date
Application number
PCT/JP2008/073125
Other languages
English (en)
French (fr)
Inventor
Takanori Kubo
Hideki Ohba
Kazuo Sakurai
Jusaku Minari
Atsushi Uno
Original Assignee
National Institute Of Advanced Industrial Science And Technology
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 National Institute Of Advanced Industrial Science And Technology filed Critical National Institute Of Advanced Industrial Science And Technology
Priority to JP2009546298A priority Critical patent/JP5354604B2/ja
Priority to US12/808,504 priority patent/US10738304B2/en
Priority to EP08862702.1A priority patent/EP2226384B1/en
Priority to CN2008801247235A priority patent/CN101918554B/zh
Priority to ES08862702.1T priority patent/ES2566477T3/es
Publication of WO2009078470A1 publication Critical patent/WO2009078470A1/ja
Priority to US16/915,433 priority patent/US20210054373A1/en

Links

Classifications

    • 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
    • C12N15/111General methods applicable to biologically active non-coding nucleic acids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • C07H21/04Compounds 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
    • CCHEMISTRY; METALLURGY
    • C08ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08BPOLYSACCHARIDES; DERIVATIVES THEREOF
    • C08B37/00Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
    • 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
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • 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
    • C12N2310/35Nature of the modification
    • C12N2310/351Conjugate
    • C12N2310/3519Fusion with another nucleic acid
    • 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
    • C12N2320/00Applications; Uses
    • C12N2320/30Special therapeutic applications
    • C12N2320/32Special delivery means, e.g. tissue-specific
    • 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
    • C12N2320/00Applications; Uses
    • C12N2320/50Methods for regulating/modulating their activity
    • C12N2320/51Methods for regulating/modulating their activity modulating the chemical stability, e.g. nuclease-resistance

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Organic Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • General Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicinal Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Materials Engineering (AREA)
  • Veterinary Medicine (AREA)
  • Pathology (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Immunology (AREA)
  • Public Health (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Polymers & Plastics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Saccharide Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

 本発明の目的は、RNA干渉効果を奏する2本鎖RNAに対して、RNA干渉効果の減弱を伴うことなく、細胞導入性及び分解酵素耐性が向上している新規な二本鎖RNAを提供することである。  β-1,3-グルカン骨格を有する多糖と2本鎖RNAの複合体において、以下の(i)~(iii)を充足させることにより、RNA干渉効果を有効に保持したまま、細胞導入性及び分解酵素耐性が顕著に向上させることができる(i)前記2本鎖RNAが、標的遺伝子中の標的配列に相補的な塩基配列からなるセンス鎖、及び該センス鎖に相補的な塩基配列を有するアンチセンス鎖を有し、且つ前記標的遺伝子の発現を抑制できる2本鎖RNAである。(ii)前記2本鎖RNAには、前記センス鎖及びアンチセンス鎖の少なくとも一方の末端に、直接又はリンカーを介して、1本鎖ポリデオキシアデニンが結合している。(iii)前記多糖と前記1本鎖ポリデオキシアデニンが複合化している。
PCT/JP2008/073125 2007-12-18 2008-12-18 多糖/2本鎖rna複合体 WO2009078470A1 (ja)

Priority Applications (6)

Application Number Priority Date Filing Date Title
JP2009546298A JP5354604B2 (ja) 2007-12-18 2008-12-18 多糖/2本鎖rna複合体
US12/808,504 US10738304B2 (en) 2007-12-18 2008-12-18 Complex of polysaccharide and double-stranded RNA
EP08862702.1A EP2226384B1 (en) 2007-12-18 2008-12-18 Complex of polysaccharide and double-stranded rna
CN2008801247235A CN101918554B (zh) 2007-12-18 2008-12-18 多糖/双链rna复合物
ES08862702.1T ES2566477T3 (es) 2007-12-18 2008-12-18 Complejo de polisacárido y ARN bicatenario
US16/915,433 US20210054373A1 (en) 2007-12-18 2020-06-29 Complex of polysaccharide and double-stranded rna and method of inhibiting expression of a target gene in a cell

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2007-326510 2007-12-18
JP2007326510 2007-12-18

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US12/808,504 A-371-Of-International US10738304B2 (en) 2007-12-18 2008-12-18 Complex of polysaccharide and double-stranded RNA
US16/915,433 Continuation US20210054373A1 (en) 2007-12-18 2020-06-29 Complex of polysaccharide and double-stranded rna and method of inhibiting expression of a target gene in a cell

Publications (1)

Publication Number Publication Date
WO2009078470A1 true WO2009078470A1 (ja) 2009-06-25

Family

ID=40795583

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP2008/073125 WO2009078470A1 (ja) 2007-12-18 2008-12-18 多糖/2本鎖rna複合体

Country Status (6)

Country Link
US (2) US10738304B2 (ja)
EP (1) EP2226384B1 (ja)
JP (1) JP5354604B2 (ja)
CN (1) CN101918554B (ja)
ES (1) ES2566477T3 (ja)
WO (1) WO2009078470A1 (ja)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012020795A1 (ja) * 2010-08-10 2012-02-16 ナパジェン ファーマ,インコーポレテッド 核酸多糖複合体
WO2012117855A1 (ja) 2011-02-28 2012-09-07 ナパジェン ファーマ,インコーポレテッド 核酸多糖複合体
WO2013021784A1 (ja) 2011-08-10 2013-02-14 ナパジェン ファーマ,インコーポレテッド 免疫寛容誘導剤
WO2013191223A1 (ja) * 2012-06-20 2013-12-27 独立行政法人科学技術振興機構 核酸複合体および核酸多糖複合体
WO2017217531A1 (ja) * 2016-06-16 2017-12-21 ナパジェン ファーマ,インコーポレテッド 核酸と抗原ペプチドの結合体
WO2018097296A1 (ja) 2016-11-28 2018-05-31 ナパジェン ファーマ,インコーポレテッド 化学修飾siRNA
WO2019230898A1 (ja) 2018-05-30 2019-12-05 ナパジェン ファーマ,インコーポレテッド 化学修飾siRNAとシゾフィランとの複合体を含む医薬組成物

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014122648A1 (en) 2013-02-05 2014-08-14 B. G. Negev Technologies And Applications Ltd. Positively charged polysaccharides for rna transfection
CN107630015B (zh) * 2016-07-19 2021-03-09 上海市东方医院 一种稳定的dna-rna双链结构
CN110951723B (zh) * 2019-12-06 2023-12-12 天津大学 一种纯dna双链缠结水凝胶及制备方法及应用
CN113045682B (zh) * 2021-03-11 2022-06-21 内蒙古大学 一种阳离子多糖及其制备方法与应用
US20240115595A1 (en) * 2022-09-08 2024-04-11 Team Medical, Llc Material compositions and methods of use improving rna stability

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996014873A2 (en) 1994-11-16 1996-05-23 Sri International COVALENTLY BOUND β-GLUCAN CONJUGATES IN TARGETED DELIVERY
WO2001034207A1 (fr) 1999-11-10 2001-05-17 Japan Science And Technology Corporation Supports de genes
JP2004261024A (ja) * 2003-02-28 2004-09-24 Japan Science & Technology Agency ペプチド修飾多糖類を用いる遺伝子治療剤
JP2005204612A (ja) 2004-01-26 2005-08-04 Japan Science & Technology Agency 新規な遺伝子導入法
JP2005255750A (ja) * 2004-03-10 2005-09-22 Japan Science & Technology Agency ポリエチレングリコールまたはポリプロピレングリコール修飾β−1,3−グルカン系遺伝子キャリアー
JP2006069913A (ja) 2004-08-31 2006-03-16 Japan Science & Technology Agency ハイブリッド多糖系キャリアーを用いる核酸類の導入方法。

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2009514877A (ja) * 2005-11-04 2009-04-09 エムディーアールエヌエー,インコーポレイテッド siRNAの送達媒体としてのペプチド−ダイザ基質RNA抱合体
AU2006325030B2 (en) 2005-12-16 2012-07-26 Cellectis Cell penetrating peptide conjugates for delivering nucleic acids into cells

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996014873A2 (en) 1994-11-16 1996-05-23 Sri International COVALENTLY BOUND β-GLUCAN CONJUGATES IN TARGETED DELIVERY
WO2001034207A1 (fr) 1999-11-10 2001-05-17 Japan Science And Technology Corporation Supports de genes
JP2004261024A (ja) * 2003-02-28 2004-09-24 Japan Science & Technology Agency ペプチド修飾多糖類を用いる遺伝子治療剤
JP2005204612A (ja) 2004-01-26 2005-08-04 Japan Science & Technology Agency 新規な遺伝子導入法
JP2005255750A (ja) * 2004-03-10 2005-09-22 Japan Science & Technology Agency ポリエチレングリコールまたはポリプロピレングリコール修飾β−1,3−グルカン系遺伝子キャリアー
JP2006069913A (ja) 2004-08-31 2006-03-16 Japan Science & Technology Agency ハイブリッド多糖系キャリアーを用いる核酸類の導入方法。

Non-Patent Citations (14)

* Cited by examiner, † Cited by third party
Title
A.C.S., vol. 38, no. 1, 1997, pages 253
CARBOHYDRATE RESEARCH, vol. 89, 1981, pages 121 - 135
HASEGAWA, ONCOLOGY AND CHEMOTHERAPY, vol. 8, 1992, pages 225
J. ROSSI ET AL., NATURE BIOTECH., vol. 23, 2005, pages 222 - 226
KAZUO SAKURAI, POLYM. PREPRINTS, JPN., vol. 49, 2000, pages 4054
KAZUO SAKURAI, POLYM. PREPRINTS. JPN., vol. 49, 2000, pages 4054
MATSUMOTO TAKAHIRO ET AL., BIOCHIM BIOPHYS ACTA, vol. 1670, no. 2, 2004, pages 91 - 104
NAGASAKI TAKESHI ET AL., BIOCONJUGATE CHEMISTRY, vol. 15, 2004, pages 249 - 259
RYOUJI KARINAGA, BIOMATERIALS, vol. 26, no. 23, August 2005 (2005-08-01), pages 4866 - 73
See also references of EP2226384A4 *
TAKAHISA ANADA ET AL., JOURNAL OF CONTROLLED RELEASE, vol. 108, no. 2-3, 28 November 2005 (2005-11-28), pages 529 - 539
THERESA M. ET AL., J. AM. CHEM. SOC., vol. 120, 1998, pages 6909
UI-TEI ET AL., NUCLEIC ACIDS RES., vol. 32, 2004, pages 936 - 948
WILLMENT J. A. ET AL.: "Charactarization of the Human beta-Glucan Receptor and Its Alternatively Spliced Isoforms", J. BIOL. CHEM., vol. 276, no. 47, 2001, pages 43818 - 43823 *

Cited By (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPWO2012020795A1 (ja) * 2010-08-10 2013-10-28 ナパジェン ファーマ, インコーポレテッドNapaJen Pharma, Inc. 核酸多糖複合体
WO2012020795A1 (ja) * 2010-08-10 2012-02-16 ナパジェン ファーマ,インコーポレテッド 核酸多糖複合体
US9713636B2 (en) 2011-02-28 2017-07-25 Napajen Pharma, Inc. Nucleic acid/polysaccharide complex
JP6124785B2 (ja) * 2011-02-28 2017-05-10 ナパジェン ファーマ, インコーポレテッドNapaJen Pharma, Inc. 核酸多糖複合体
US9801929B2 (en) 2011-02-28 2017-10-31 Napajen Pharma, Inc. Immune tolerance inducer
JPWO2012117855A1 (ja) * 2011-02-28 2014-07-07 ナパジェン ファーマ, インコーポレテッドNapaJen Pharma, Inc. 核酸多糖複合体
WO2012117855A1 (ja) 2011-02-28 2012-09-07 ナパジェン ファーマ,インコーポレテッド 核酸多糖複合体
JPWO2013021784A1 (ja) * 2011-08-10 2015-03-05 ナパジェン ファーマ, インコーポレテッドNapaJen Pharma, Inc. 免疫寛容誘導剤
WO2013021784A1 (ja) 2011-08-10 2013-02-14 ナパジェン ファーマ,インコーポレテッド 免疫寛容誘導剤
CN104471063A (zh) * 2012-06-20 2015-03-25 独立行政法人科学技术振兴机构 核酸复合物及核酸多糖复合物
JPWO2013191223A1 (ja) * 2012-06-20 2016-05-26 国立研究開発法人科学技術振興機構 核酸複合体および核酸多糖複合体
WO2013191223A1 (ja) * 2012-06-20 2013-12-27 独立行政法人科学技術振興機構 核酸複合体および核酸多糖複合体
WO2017217531A1 (ja) * 2016-06-16 2017-12-21 ナパジェン ファーマ,インコーポレテッド 核酸と抗原ペプチドの結合体
JPWO2017217531A1 (ja) * 2016-06-16 2019-04-04 ナパジェン ファーマ, インコーポレテッドNapaJen Pharma, Inc. 核酸と抗原ペプチドの結合体
WO2018097296A1 (ja) 2016-11-28 2018-05-31 ナパジェン ファーマ,インコーポレテッド 化学修飾siRNA
JPWO2018097296A1 (ja) * 2016-11-28 2018-11-29 ナパジェン ファーマ, インコーポレテッドNapaJen Pharma, Inc. 化学修飾siRNA
JP2019089820A (ja) * 2016-11-28 2019-06-13 ナパジェン ファーマ, インコーポレテッドNapaJen Pharma, Inc. 化学修飾siRNA
US11203755B2 (en) 2016-11-28 2021-12-21 Napajen Pharma, Inc. Chemically-modified siRNA
JP7100367B2 (ja) 2016-11-28 2022-07-13 ナパジェン ファーマ,インコーポレテッド 化学修飾siRNA
WO2019230898A1 (ja) 2018-05-30 2019-12-05 ナパジェン ファーマ,インコーポレテッド 化学修飾siRNAとシゾフィランとの複合体を含む医薬組成物

Also Published As

Publication number Publication date
US20210054373A1 (en) 2021-02-25
ES2566477T3 (es) 2016-04-13
US10738304B2 (en) 2020-08-11
EP2226384A1 (en) 2010-09-08
JP5354604B2 (ja) 2013-11-27
US20110111501A1 (en) 2011-05-12
CN101918554B (zh) 2013-07-03
CN101918554A (zh) 2010-12-15
EP2226384A4 (en) 2011-03-30
JPWO2009078470A1 (ja) 2011-04-28
EP2226384B1 (en) 2016-03-02

Similar Documents

Publication Publication Date Title
WO2009078470A1 (ja) 多糖/2本鎖rna複合体
WO2006073601A3 (en) Methods and compositions for rna interference
WO2006078414A3 (en) METHODS AND COMPOSITIONS CONCERNING siRNA'S AS MEDIATORS OF RNA INTERFERENCE
WO2007115168A3 (en) Compositions and methods for inhibiting expression of eg5 gene
WO2011056005A3 (ko) 안티센스 가닥에 의한 오프-타겟 효과를 최소화한 신규한 siRNA 구조 및 그 용도
WO2010018563A3 (en) Compositions and methods for the prognosis of lymphoma
WO2009142822A3 (en) 2-f modified rna interference agents
WO2011032034A3 (en) Nucleobase-functionalized conformationally restricted nucleotides and oligonucleotides for targeting nucleic acids
AU2008339215A8 (en) Novel siRNA structure for minimizing off-target effects and relaxing saturation of RNAi machinery and the use thereof
WO2009045457A3 (en) Tripartite rnai constructs
WO2007128477A3 (en) SHORT INTERFERING RIBONUCLEIC ACID (siRNA) FOR ORAL ADMINISTRATION
EA201100811A1 (ru) Фармацевтическая композиция
WO2007134161A8 (en) Compositions and methods for inhibiting expression of the pcsk9 gene
WO2008109369A8 (en) Nucleic acid compounds for inhibiting tnf gene expression and uses thereof
WO2011128444A3 (en) Capping-prone rna polymerase enzymes and their applications
WO2009102427A3 (en) Modified rnai polynucleotides and uses thereof
WO2006104891A3 (en) Methods and genetic constructs for modification of lignin composition of corn cobs
MX2010003722A (es) Variantes de glucoamilasa.
WO2008008719A3 (en) Compositions and methods for inhibiting expression of the myc gene
WO2005097205A8 (en) Dna virus microrna and methods for inhibiting same
WO2012177949A3 (en) Compositions and methods for inhibition of expression of protein c (proc) genes
WO2010013815A1 (ja) 標的遺伝子の発現を抑制する組成物
WO2009086428A3 (en) Methods and compositions for increasing gene expression
WO2007127919A3 (en) Compositions and methods for inhibiting expression of a gene from the jc virus
WO2010006973A3 (en) Compositions and methods for inhibiting expression of tgf-beta receptor genes

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 200880124723.5

Country of ref document: CN

121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 08862702

Country of ref document: EP

Kind code of ref document: A1

ENP Entry into the national phase

Ref document number: 2009546298

Country of ref document: JP

Kind code of ref document: A

NENP Non-entry into the national phase

Ref country code: DE

WWE Wipo information: entry into national phase

Ref document number: 2008862702

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 12808504

Country of ref document: US