CN112119159B - micro-RNA和肥胖 - Google Patents

micro-RNA和肥胖 Download PDF

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Publication number
CN112119159B
CN112119159B CN201980032204.4A CN201980032204A CN112119159B CN 112119159 B CN112119159 B CN 112119159B CN 201980032204 A CN201980032204 A CN 201980032204A CN 112119159 B CN112119159 B CN 112119159B
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CN112119159A (zh
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P·P·潘多雷尔
R·潘内拉
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Beth Israel Deaconess Medical Center Inc
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/713—Double-stranded nucleic acids or oligonucleotides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
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    • 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
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    • 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
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    • 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
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    • 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]
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • 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]
    • C12N2310/141—MicroRNAs, miRNAs
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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    • 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
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    • 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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    • C12N2320/00—Applications; Uses
    • C12N2320/50—Methods for regulating/modulating their activity

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  • General Engineering & Computer Science (AREA)
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  • Plant Pathology (AREA)
  • Biophysics (AREA)
  • Physics & Mathematics (AREA)
  • Microbiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Diabetes (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Child & Adolescent Psychology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Peptides Or Proteins (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
CN201980032204.4A 2018-03-14 2019-03-14 micro-RNA和肥胖 Active CN112119159B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201862642934P 2018-03-14 2018-03-14
US62/642,934 2018-03-14
PCT/US2019/022350 WO2019178410A1 (en) 2018-03-14 2019-03-14 Micro-rna and obesity

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CN112119159A CN112119159A (zh) 2020-12-22
CN112119159B true CN112119159B (zh) 2025-04-29

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CN201980018587.XA Active CN111918968B (zh) 2018-03-14 2019-03-14 Micro-RNA 22的抑制剂

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US (2) US11753639B2 (https=)
EP (2) EP3765610A4 (https=)
JP (2) JP7318166B2 (https=)
KR (2) KR20200131287A (https=)
CN (2) CN112119159B (https=)
AU (2) AU2019234917B2 (https=)
BR (2) BR112020018705A2 (https=)
CA (2) CA3093572A1 (https=)
ES (1) ES3001019T3 (https=)
RU (2) RU2020131372A (https=)
SG (2) SG11202008925VA (https=)
WO (2) WO2019178410A1 (https=)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20200131287A (ko) 2018-03-14 2020-11-23 베스 이스라엘 데코니스 메디칼 센터 마이크로-rna 22의 억제제
CN110609142A (zh) * 2019-10-09 2019-12-24 广州医科大学附属第二医院 一种检测外周血fto蛋白与自身调控元件结合能力的方法与应用
CN115029347B (zh) * 2022-05-11 2024-02-20 珠海中科先进技术研究院有限公司 识别和调控肝肾细胞纤维化的分子监测序列、重组质粒、抑制病毒
CN116082447A (zh) * 2022-09-09 2023-05-09 湖南大学 一种多肽及其制备方法
CN117304258B (zh) * 2022-09-09 2024-09-24 湖南大学 一种多肽的用途
EP4353823A1 (en) * 2022-10-12 2024-04-17 Resalis Therapeutics S.r.l. Inhibitors of micro-rna 22

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017187426A1 (en) * 2016-04-29 2017-11-02 Aptamir Therapeutics, Inc. Inhibition of mir-22 mirna by apt-110

Family Cites Families (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5981505A (en) 1993-01-26 1999-11-09 The Trustees Of The University Of Pennsylvania Compositions and methods for delivery of genetic material
US5837533A (en) 1994-09-28 1998-11-17 American Home Products Corporation Complexes comprising a nucleic acid bound to a cationic polyamine having an endosome disruption agent
US5840710A (en) 1994-12-09 1998-11-24 Genzyme Corporation Cationic amphiphiles containing ester or ether-linked lipophilic groups for intracellular delivery of therapeutic molecules
US6217900B1 (en) 1997-04-30 2001-04-17 American Home Products Corporation Vesicular complexes and methods of making and using the same
CA2294988C (en) 1997-07-01 2015-11-24 Isis Pharmaceuticals Inc. Compositions and methods for the delivery of oligonucleotides via the alimentary canal
JP2002516256A (ja) 1998-05-26 2002-06-04 アイ・シー・エヌ・フアーマシユーテイカルズ・インコーポレイテツド 二環式糖成分を有する新規ヌクレオシド
US6838283B2 (en) 1998-09-29 2005-01-04 Isis Pharmaceuticals Inc. Antisense modulation of survivin expression
US6693187B1 (en) 2000-10-17 2004-02-17 Lievre Cornu Llc Phosphinoamidite carboxlates and analogs thereof in the synthesis of oligonucleotides having reduced internucleotide charge
CA2487274A1 (en) 2002-05-06 2003-11-13 Nucleonics Inc. Spermine chemically linked to lipids and cell-specific targeting molecules as a transfection agent
EP2302055B1 (en) * 2004-11-12 2014-08-27 Asuragen, Inc. Methods and compositions involving miRNA and miRNA inhibitor molecules
US20070213292A1 (en) * 2005-08-10 2007-09-13 The Rockefeller University Chemically modified oligonucleotides for use in modulating micro RNA and uses thereof
KR101485071B1 (ko) * 2005-12-12 2015-01-26 더 유니버시티 오브 노쓰 캐롤라이나 엣 채플 힐 마이크로 ｒｎａ를 이용한 근육 세포 증식 및 분화 조절방법과 근육 세포 치료방법 및 유전자 발현 억제방법그리고 마이크로 ｒｎａ 분자의 발현용 벡터와 이를 이용한키트 및 미오사이트
AU2013254923A1 (en) * 2006-04-03 2013-11-28 Santaris Pharma A/S Pharmaceutical compositions comprising anti-miRNA antisense oligonucleotide
EP2007888A2 (en) 2006-04-03 2008-12-31 Santaris Pharma A/S Pharmaceutical composition comprising anti-mirna antisense oligonucleotides
EP2623599B1 (en) * 2007-10-04 2019-01-02 Roche Innovation Center Copenhagen A/S Micromirs
EP2419537B1 (en) * 2009-04-13 2014-01-29 Somagenics, Inc. Methods and compositions for detection of small rnas
SG176716A1 (en) * 2009-06-08 2012-01-30 Miragen Therapeutics CHEMICAL MODIFICATION MOTIFS FOR miRNA INHIBITORS AND MIMETICS
UY33807A (es) * 2010-12-17 2012-07-31 Sanofi Sa miRNAs como indicadores del estado tisular o de enfermedades como osteoartritis
CA2832899A1 (en) 2011-04-12 2012-10-18 Beth Israel Deaconess Medical Center, Inc. Micro-rna inhibitors and their uses in disease
JP6092655B2 (ja) * 2012-02-23 2017-03-08 善基 村上 テスト体液サンプルの分類方法
US9034839B2 (en) 2012-04-20 2015-05-19 Aptamir Therapeutics, Inc. miRNA modulators of thermogenesis
WO2013181613A1 (en) * 2012-05-31 2013-12-05 Research Development Foundation Mirna for the diagnosis and treatment of autoimmune and inflammatory disease
CN107236735B (zh) * 2012-06-21 2019-11-08 米拉根医疗股份有限公司 包含锁核酸基序的基于寡核苷酸的抑制剂
US9822358B2 (en) 2013-10-18 2017-11-21 Beth Israel Deaconess Medical Center Treatment of cancers with micro-RNA inhibitors
CA2935426C (en) * 2014-01-30 2023-07-25 F. Hoffmann-La Roche Ag Polyoligomer compound with biocleavable conjugates for reducing or inhibiting expression of a nucleic acid target
WO2016127002A1 (en) 2015-02-04 2016-08-11 Bristol-Myers Squibb Company Lna oligonucleotides with alternating flanks
WO2016149358A1 (en) * 2015-03-16 2016-09-22 Duncan Ross Method of treatment comprising membrane-enclosed vesicle
CN107432933A (zh) * 2017-07-13 2017-12-05 中南大学湘雅三医院 miR‑22作为靶位点在制备膀胱癌的化疗增敏治疗药物中的应用
WO2019053235A1 (en) * 2017-09-15 2019-03-21 Genfit NON-INVASIVE DIAGNOSIS OF NON ALCOHOLIC LIVER DISEASES, NON ALCOHOLIC STHEATHEPATITIS AND / OR HEPATIC FIBROSIS
KR20200131287A (ko) 2018-03-14 2020-11-23 베스 이스라엘 데코니스 메디칼 센터 마이크로-rna 22의 억제제
WO2019217907A1 (en) * 2018-05-11 2019-11-14 The Regents Of The University Of California Methods and compositions for the treatment of hepatic and metabolic diseases

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017187426A1 (en) * 2016-04-29 2017-11-02 Aptamir Therapeutics, Inc. Inhibition of mir-22 mirna by apt-110

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
miR-22靶向SIRT1促进人脂肪肝细胞中脂肪沉积的机制研究;郑晓筠等;《胃肠病学和肝病学杂志》;第27卷(第2期);第182页摘要、第183段左栏第3段 *
郑晓筠等.miR-22靶向SIRT1促进人脂肪肝细胞中脂肪沉积的机制研究.《胃肠病学和肝病学杂志》.2018,第27卷(第2期),第182页摘要、第183段左栏第3段. *

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US11499152B2 (en) 2022-11-15
CA3093572A1 (en) 2019-09-19
CN111918968A (zh) 2020-11-10
SG11202008925VA (en) 2020-10-29
JP2021518841A (ja) 2021-08-05
EP3765619A1 (en) 2021-01-20
AU2019234917B2 (en) 2025-06-26
AU2019234917A1 (en) 2020-10-01
CA3093844A1 (en) 2019-09-19
CN111918968B (zh) 2023-11-24
EP3765619B1 (en) 2024-10-09
AU2019234916B2 (en) 2025-06-26
WO2019178410A1 (en) 2019-09-19
AU2019234916A1 (en) 2020-10-15
EP3765610A4 (en) 2022-01-19
RU2020131372A (ru) 2022-04-14
JP7318166B2 (ja) 2023-08-01
EP3765610A1 (en) 2021-01-20
BR112020018752A2 (pt) 2021-01-05
EP3765619A4 (en) 2021-12-08
KR20200132920A (ko) 2020-11-25
RU2020132725A (ru) 2022-04-15
KR20200131287A (ko) 2020-11-23
JP2021518159A (ja) 2021-08-02
EP3765619C0 (en) 2024-10-09
US20210017520A1 (en) 2021-01-21
CN112119159A (zh) 2020-12-22
ES3001019T3 (es) 2025-03-04
SG11202008921YA (en) 2020-10-29
WO2019178411A1 (en) 2019-09-19
BR112020018705A2 (pt) 2021-01-05
US11753639B2 (en) 2023-09-12
US20210017521A1 (en) 2021-01-21

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