CN104955950B - 具有改善的脱靶特征谱的寡核苷酸 - Google Patents

具有改善的脱靶特征谱的寡核苷酸 Download PDF

Info

Publication number
CN104955950B
CN104955950B CN201380057694.6A CN201380057694A CN104955950B CN 104955950 B CN104955950 B CN 104955950B CN 201380057694 A CN201380057694 A CN 201380057694A CN 104955950 B CN104955950 B CN 104955950B
Authority
CN
China
Prior art keywords
oligomer
monomer
affinity
region
target
Prior art date
Legal status (The legal status 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 status listed.)
Active
Application number
CN201380057694.6A
Other languages
English (en)
Chinese (zh)
Other versions
CN104955950A (zh
Inventor
T·莫勒
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Guangdong Maijinjia Biotechnology Co Ltd
Original Assignee
MIRRX THERAPEUTICS
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 MIRRX THERAPEUTICS filed Critical MIRRX THERAPEUTICS
Publication of CN104955950A publication Critical patent/CN104955950A/zh
Application granted granted Critical
Publication of CN104955950B publication Critical patent/CN104955950B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • 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
    • C12N15/1131—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 viruses
    • 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
    • C12N2310/11—Antisense
    • 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
    • C12N2310/113—Antisense targeting other non-coding nucleic acids, e.g. antagomirs
    • 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
    • C12N2310/31—Chemical structure of the backbone
    • C12N2310/315—Phosphorothioates
    • 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
    • C12N2310/34—Spatial arrangement of the modifications
    • C12N2310/341—Gapmers, i.e. of the type ===---===
    • 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
    • C12N2320/53—Methods for regulating/modulating their activity reducing unwanted side-effects

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Biotechnology (AREA)
  • General Engineering & Computer Science (AREA)
  • Zoology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Wood Science & Technology (AREA)
  • Microbiology (AREA)
  • Plant Pathology (AREA)
  • Biophysics (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Physics & Mathematics (AREA)
  • Virology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
CN201380057694.6A 2012-09-26 2013-09-26 具有改善的脱靶特征谱的寡核苷酸 Active CN104955950B (zh)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201261705668P 2012-09-26 2012-09-26
US61/705,668 2012-09-26
DKPA201200587 2012-09-26
DKPA201200587 2012-09-26
PCT/DK2013/050308 WO2014048441A1 (en) 2012-09-26 2013-09-26 Oligomers with improved off-target profile

Publications (2)

Publication Number Publication Date
CN104955950A CN104955950A (zh) 2015-09-30
CN104955950B true CN104955950B (zh) 2019-04-26

Family

ID=50387035

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201380057694.6A Active CN104955950B (zh) 2012-09-26 2013-09-26 具有改善的脱靶特征谱的寡核苷酸

Country Status (7)

Country Link
US (1) US9725721B2 (OSRAM)
EP (1) EP2900822B1 (OSRAM)
JP (1) JP6352269B2 (OSRAM)
CN (1) CN104955950B (OSRAM)
AU (1) AU2013324716B2 (OSRAM)
CA (1) CA2886116C (OSRAM)
WO (1) WO2014048441A1 (OSRAM)

Families Citing this family (34)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103620035B (zh) 2011-04-25 2021-04-23 赛诺菲 用于调节mir-21活性的微rna化合物以及方法
BR112014026639A8 (pt) 2012-04-25 2018-01-16 Regulus Therapeutics Inc compostos , métodos de inibição da atividade de mir-21 , método para diminuir a expressão de colágeno , método para tratar , prevenir ou atrasar o início de uma doença , método de tratamento de um distúrbio fibroproliferativo e usos de um composto.
US9879255B2 (en) 2012-10-02 2018-01-30 University Of Newcastle Upon Tyne Modulation of RNA activity and vascular permeability
UA116639C2 (uk) 2012-10-09 2018-04-25 Рег'Юлес Терап'Ютікс Інк. Способи лікування синдрому альпорта
NZ630890A (en) 2013-05-01 2017-09-29 Regulus Therapeutics Inc Microrna compounds and methods for modulating mir-122
EP3060664B1 (en) 2013-10-25 2021-07-07 Sanofi Microrna compounds and methods for modulating mir-21 activity
CN113151468B (zh) 2014-06-13 2024-11-26 东丽株式会社 乳癌的检测试剂盒或装置以及检测方法
KR20250030013A (ko) * 2014-06-13 2025-03-05 도레이 카부시키가이샤 대장암의 검출 키트 또는 디바이스 및 검출 방법
RU2017101023A (ru) * 2014-06-16 2018-07-16 Торэй Индастриз, Инк. Набор или устройство для обнаружения рака желудка и способ обнаружения
RU2017101174A (ru) 2014-06-18 2018-07-18 Торэй Индастриз, Инк. Набор или устройство для обнаружения рака печени и способ обнаружения
JP6385732B2 (ja) * 2014-06-27 2018-09-05 国立大学法人北海道大学 免疫応答制御剤
JP2017523790A (ja) 2014-08-07 2017-08-24 レグルス セラピューティクス インコーポレイテッド 代謝障害のためのマイクロｒｎａの標的化
CN107075578B (zh) * 2014-09-16 2021-06-01 东丽株式会社 miRNA表达量的比较分析方法和装置
WO2016115609A1 (en) * 2015-01-20 2016-07-28 Katholieke Universiteit Leuven Colon cancer
RU2686313C2 (ru) 2015-02-25 2019-04-25 Байонир Корпорейшн Фармацевтическая композиция для лечения рака, содержащая микроРНК в качестве активного ингредиента
CN104826133B (zh) * 2015-05-01 2020-11-24 北京博奥医学检验所有限公司 一种与肺腺癌有关的miRNA及其药物组合物
CN107058472B (zh) * 2016-11-03 2020-10-27 中国人民解放军陆军军医大学 一种通过四种血浆microRNA联合诊断急性高山病的诊断试剂盒
CN107058474B (zh) * 2016-11-03 2020-09-01 中国人民解放军陆军军医大学 一种通过血浆microRNA-3591-3p诊断急性高山病的诊断试剂盒
CN107058475B (zh) * 2016-11-03 2020-10-27 中国人民解放军陆军军医大学 一种联合miR-676、miR-181b和miR-193b诊断急性高山病的试剂盒
CN107058471B (zh) * 2016-11-03 2020-09-01 中国人民解放军陆军军医大学 一种通过四种microRNA生物标志物联合预测急性高山病发病风险的试剂盒
CN107058470B (zh) * 2016-11-03 2020-09-01 中国人民解放军陆军军医大学 一种通过联合miR-136和miR-4791预测急性高山病发病风险的诊断试剂盒
CN107058473B (zh) * 2016-11-03 2020-10-27 中国人民解放军陆军军医大学 一种联合miR-676、miR-181b和miR-3591诊断急性高山病的试剂盒
CN108251422A (zh) * 2016-12-29 2018-07-06 昆山彭济凯丰生物科技有限公司 通过miR-6069进行抗癌的方法和药物及其应用
CN108295260A (zh) * 2017-01-13 2018-07-20 彭长庚 通过miR-1915-3p进行抗癌的方法和药物及其应用
CN108295086B (zh) * 2017-01-13 2021-11-02 昆山彭济凯丰生物科技有限公司 通过miR-4418进行抗癌的方法和药物及其应用
CN108310381A (zh) * 2017-01-16 2018-07-24 昆山彭济凯丰生物科技有限公司 通过miR-6511b-3p进行抗癌的方法和药物及其应用
CN107502609A (zh) * 2017-09-08 2017-12-22 中国科学院深圳先进技术研究院 一种靶向cJun信号通路的miRNA及其制备方法和应用
KR102070969B1 (ko) * 2018-04-10 2020-01-29 한국한의학연구원 통증 판별용 마커
WO2019217369A1 (en) 2018-05-08 2019-11-14 Regulus Therapeutics Inc. Galnac conjugated modified oligonucleotide as mir-122 inhibitor having hcv antiviral activity with reduced hyperbilirubinemia side-effect
CN109468375B (zh) * 2018-12-28 2021-05-14 固安博健生物技术有限公司 分子标志物在骨质疏松症中的应用
CN113993588B (zh) * 2019-06-05 2024-03-01 癌症干细胞科技公司 癌治疗剂
CN111073973A (zh) * 2019-12-10 2020-04-28 石河子大学 一种用于早期诊断2型糖尿病的microRNA序列及其应用
CN114767703B (zh) * 2022-06-20 2022-09-02 山东恺悌生物制品有限公司 miR-4311模拟物在制备肺癌治疗药物中的应用
WO2025067351A2 (en) * 2023-09-27 2025-04-03 Neuro3 Therapeutics, Inc. Novel sirna constructs, therapeutics, and modifications

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008074328A2 (en) * 2006-12-21 2008-06-26 Exiqon A/S Microrna target site blocking oligos and uses thereof

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5898031A (en) * 1996-06-06 1999-04-27 Isis Pharmaceuticals, Inc. Oligoribonucleotides for cleaving RNA
EP1706489B9 (en) 2003-12-23 2011-01-05 Santaris Pharma A/S Oligomeric compounds for the modulation of bcl-2
WO2007031081A2 (en) * 2005-09-15 2007-03-22 Santaris Pharma A/S RNA ANTAGONIST COMPOUNDS FOR THE INHIBITION OF APO-Bl00 EXPRESSION
US20100021914A1 (en) * 2006-11-23 2010-01-28 Querdenker Aps Oligonucleotides for modulating target rna activity
CN101821390A (zh) 2007-06-14 2010-09-01 米尔克斯治疗有限责任公司 用于调节靶rna活性的寡核苷酸
TW200930382A (en) 2007-11-26 2009-07-16 Santaris Pharma As LNA antagonists targeting the androgen receptor
WO2009090182A1 (en) 2008-01-14 2009-07-23 Santaris Pharma A/S C4'-substituted - dna nucleotide gapmer oligonucleotides
JP5773535B2 (ja) 2009-04-24 2015-09-02 ロシュ・イノベーション・センター・コペンハーゲン・アクティーゼルスカブＲｏｃｈｅ Ｉｎｎｏｖａｔｉｏｎ Ｃｅｎｔｅｒ Ｃｏｐｅｎｈａｇｅｎ Ａ／Ｓ インターフェロンに非応答性のｈｃｖ患者の治療のための医薬組成物
US9193752B2 (en) * 2010-03-17 2015-11-24 Isis Pharmaceuticals, Inc. 5′-substituted bicyclic nucleosides and oligomeric compounds prepared therefrom
US20130079505A1 (en) 2010-03-24 2013-03-28 Mirrx Therapeutics A/S Bivalent antisense oligonucleotides

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008074328A2 (en) * 2006-12-21 2008-06-26 Exiqon A/S Microrna target site blocking oligos and uses thereof

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
chemical modification and design of anti-miRNA oligonucleotides;K A LENNOX，et al;《GENE THERAPY》;20111214;第18卷(第12期);1111-1120 *
Fine-tuning of ENA gapmers as antisense oligonucleotides for sequence-specific inhibition;MIHO TAKAGI-SATO，et al;《OLIGONUCLEOTIDES》;20071231(第17期);291-301 *

Also Published As

Publication number Publication date
WO2014048441A1 (en) 2014-04-03
EP2900822A1 (en) 2015-08-05
JP2016513950A (ja) 2016-05-19
US9725721B2 (en) 2017-08-08
EP2900822B1 (en) 2021-11-24
EP2900822A4 (en) 2016-05-25
CA2886116C (en) 2022-06-07
JP6352269B2 (ja) 2018-07-04
CA2886116A1 (en) 2014-04-03
AU2013324716B2 (en) 2019-06-13
US20160145620A1 (en) 2016-05-26
AU2013324716A1 (en) 2015-04-09
CN104955950A (zh) 2015-09-30

Similar Documents

Publication Publication Date Title
CN104955950B (zh) 具有改善的脱靶特征谱的寡核苷酸
Faria et al. Triplex‐forming molecules: from concepts to applications
WO2009135093A3 (en) Rnase-h-based assays utilizing modified rna monomers
BRPI0811170B8 (pt) oligonucleotídeos de rna e complexos de rna substituídos por hidroximetila
WO2003070911A3 (en) Rna interference mediated inhibition of type 1 insulin-like growth factor receptor (igf-1r)
WO2008109450A4 (en) Nucleic acid compounds for inhibiting id-1 gene expression and uses thereof
EA015570B1 (ru) Фармацевтическая композиция
Shi et al. Altered expression of microRNAs in the myocardium of rats with acute myocardial infarction
WO2004078941A3 (en) Modulation of gene expression using dna-rna hybrids
JP2009531433A5 (OSRAM)
Petch et al. Messenger RNA expression profiling of genes involved in epidermal growth factor receptor signalling in human cancer cells treated with scanning array-designed antisense oligonucleotides
CN101121934A (zh) 多靶点miRNA反义核苷酸技术
ES2940189T3 (es) Método para hibridar una molécula de ácido nucleico
Patil et al. Recognition of RNA sequence and structure by duplex and triplex formation: targeting miRNA and pre-miRNA
Erdem et al. Versatile RNA: overlooked gems of the transcriptome
WO2008109548A3 (en) Nucleic acid compounds for inhibiting tgfb gene expression and uses thereof
Malina et al. Antitumor substitution-inert polynuclear platinum complexes stabilize G-quadruplex DNA and suppress G-quadruplex-mediated gene expression
US11306310B2 (en) MicroRNA inhibitor
US20190040395A1 (en) Modulators of klk3 erna
Zeng et al. Structural‐Based Stability Enhancement of Antisense DNA Oligonucleotides
TWI860394B (zh) Ｒｎａ作用抑制劑及其利用
CN119592567B (zh) 基于肿瘤剪接转换治疗的反义寡核苷酸及其应用
Wan Antisense-mediated exon skipping to shift alternative splicing to treat cancer
WO2019032054A1 (en) METHOD FOR SCREENING VARIANTS OR SPLICE EVENTS
TWI901370B (zh) Ｒｎａ作用抑制劑及其利用

Legal Events

Date Code Title Description
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant
TR01 Transfer of patent right
TR01 Transfer of patent right

Effective date of registration: 20200422

Address after: Floor 11, No. 247, science Avenue, Huangpu District, Guangzhou City, Guangdong Province

Patentee after: Guangdong maijinjia Biotechnology Co., Ltd

Address before: Tan barley ratio

Patentee before: MIRRX THERAPEUTICS