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Development of a nanoparticle to release nucleic acids in a mitochondrial environment

Research Project

Project/Area Number 15K12532
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Biomedical engineering/Biomaterial science and engineering
Research InstitutionHokkaido University

Principal Investigator

YAMADA Yuma  北海道大学, 薬学研究院, 准教授 (60451431)

Co-Investigator(Renkei-kenkyūsha) HYODO Mamoru  愛知工業大学, 工学部, 講師 (30548186)
Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords薬物送達システム / ミトコンドリア
Outline of Final Research Achievements

It was recently reported that mutations in mitochondrial DNA (mtDNA) form the basis of mitochondria (Mt) related diseases. Therefore, the delivery of nucleic acids targeting mutant mtDNA would be expected to be an innovative therapeutic strategy for such diseases. To date, we developed a MITO-Porter, a nano carrier for mitochondrial delivery. The aim of this study is to develop a nanoparticle that can release nucleic acids in response to the Mt environment following its delivery to the Mt. In this study, we evaluated nanoparticles with various Mt environment responsive peptides, and we succeeded in constructing a nanoparticle that was capable of releasing nucleic acids in response to conditions that mimic the Mt environment. In addition, we confirmed successful regulation of the mitochondrial gene expression by transfection of nanoparticles using the MITO-Porter. Our findings can contribute to development nanomedicine for mitochondrial gene therapy.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (33 results)

All 2017 2016 2015 Other

All Journal Article (7 results) (of which Peer Reviewed: 4 results,  Acknowledgement Compliant: 4 results) Presentation (17 results) (of which Int'l Joint Research: 4 results,  Invited: 6 results) Book (2 results) Remarks (6 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] MITO-Porter, Multifunctional Envelope-Type Nano Device for Mitochondrial Delivery toward Innovative Nano Medicine.2017

    • Author(s)
      Yamada Y, Harashima H.
    • Journal Title

      J. Soc. Powder Technol., Japan

      Volume: 印刷中

    • NAID

      130005606219

    • Related Report
      2016 Annual Research Report
  • [Journal Article] ミトコンドリアDDS研究のあゆみ: ミトコンドリア標的型ナノカプセル“MITO-Porter”が拓く未来医療2017

    • Author(s)
      山田勇磨
    • Journal Title

      医学のあゆみ

      Volume: 260 Pages: 42-48

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Mitochondrial DDS Opens Innovative Pharmaceutics2016

    • Author(s)
      Yuma Yamada
    • Journal Title

      YAKUGAKU ZASSHI

      Volume: 136 Issue: 1 Pages: 55-62

    • DOI

      10.1248/yakushi.15-00227-3

    • NAID

      130005115195

    • ISSN
      0031-6903, 1347-5231
    • Year and Date
      2016-01-01
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Mitochondrial delivery of antisense RNA by MITO-Porter results in mitochondrial RNA knockdown, and has a functional impact on mitochondria2015

    • Author(s)
      Ryo Furukawa, Yuma Yamada, Eriko Kawamura, Hideyoshi Harashima
    • Journal Title

      Biomaterials

      Volume: 57 Pages: 107-115

    • DOI

      10.1016/j.biomaterials.2015.04.022

    • NAID

      120006313408

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] An analysis of membrane fusion between mitochondrial double membranes and MITO-Porter, mitochondrial fusogenic vesicles2015

    • Author(s)
      Yuma Yamada, Yutaka Fukuda, Hideyoshi Harashima
    • Journal Title

      Mitochondrion

      Volume: 24 Pages: 50-55

    • DOI

      10.1016/j.mito.2015.07.003

    • NAID

      120005828499

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Validation of mitochondria gene delivery in liver and skeletal muscle via hydrodynamic injection using an artificial mitochondrial reporter DNA vecto2015

    • Author(s)
      Yukari Yasuzaki, Yuma Yamada, Takuya Ishikawa, Hideyoshi Harashima
    • Journal Title

      Molecular Pharmaceutics

      Volume: 12 Issue: 12 Pages: 4311-4320

    • DOI

      10.1021/acs.molpharmaceut.5b00511

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Mitochondrial DDS has a significant impact on the medical and life sciences: the 7th Young Researcher's Award in the 31th Annual Meeting of the Japan Society of Drug Delivery System.2015

    • Author(s)
      山田勇磨
    • Journal Title

      Drug Delivery System

      Volume: 30 Issue: 4 Pages: 348-362

    • DOI

      10.2745/dds.30.348

    • NAID

      130005116537

    • ISSN
      0913-5006, 1881-2732
    • Related Report
      2015 Research-status Report
    • Acknowledgement Compliant
  • [Presentation] ミトコンドリア標的型インテリジェントナノデバイスを用いた遺伝子治療への挑戦2016

    • Author(s)
      山田勇磨、原島秀吉
    • Organizer
      第25回 インテリジェント材料・システムシンポジウム
    • Place of Presentation
      東京女子医科大学 先端生命医科学研究所 TWIns(東京都新宿区)
    • Year and Date
      2016-01-08
    • Related Report
      2015 Research-status Report
  • [Presentation] ミトコンドリアDDSの創製と心疾患治療への展開2016

    • Author(s)
      山田勇磨
    • Organizer
      第3回iHFフォーラム
    • Place of Presentation
      ホテルオークラ東京(東京都・港区)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] ミトコンドリアDDS (Drug Delivery System) が拓く医療の未来2016

    • Author(s)
      阿部二郎、山田勇磨、武田充人、原島秀吉
    • Organizer
      北海道大学医学部・小児科・オータムセミナー2016
    • Place of Presentation
      ネストホテル札幌駅前 (北海道・札幌市)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Mitochondria: Innovative strategy to manage myocarditis using mitochondrial drug delivery system (DDS).2016

    • Author(s)
      Abe J, Yamada Y, Takeda A, Harashima H.
    • Organizer
      Asia-Pacific Pediatric Cardiology Society 6th Congress.
    • Place of Presentation
      Shanghai (China)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ミトコンドリア薬物送達システムを用いた心筋炎に対する新たな治療戦略2016

    • Author(s)
      阿部二郎、山田勇磨、武田充人、原島秀吉
    • Organizer
      第52回日本小児循環器学会総会・学術集会
    • Place of Presentation
      東京ドームホテル (東京都・文京区)
    • Related Report
      2016 Annual Research Report
  • [Presentation] ミトコンドリア標的型ナノカプセル・MITO-Porterの開発とナノバイオ研究への展開2016

    • Author(s)
      山田勇磨、原島秀吉
    • Organizer
      第五回ナノカーボンバイオシンポジウム
    • Place of Presentation
      北海道立道民活動センターかでる2.7 (北海道・札幌市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] ミトコンドリア標的型ナノカプセル・MITO-Porterを用いたミトコンドリアを標的とする疾患治療戦略の提案2016

    • Author(s)
      山田勇磨、原島秀吉
    • Organizer
      第10回 次世代を担う若手医療薬科学シンポジウム
    • Place of Presentation
      群馬大学昭和キャンパス(群馬県・前橋市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] ミトコンドリアを標的とするDDSを用いた薬剤耐性癌治療戦略の検証2016

    • Author(s)
      山田勇磨、原島秀吉
    • Organizer
      第75回日本癌学会総会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] ドキソルビシン封入ミトコンドリア標的型リポソームを用いた耐性癌治療戦略の検証2016

    • Author(s)
      宗近玲那、山田勇磨、河村恵理子、櫻井遊、佐藤悠介、原島秀吉
    • Organizer
      日本薬剤学会第31年会
    • Place of Presentation
      長良川国際会議場(岐阜県・岐阜市)
    • Related Report
      2016 Annual Research Report
  • [Presentation] ミトコンドリア標的型核酸ナノキャリアの開発および核酸医薬への展開2015

    • Author(s)
      山田勇磨、河村恵理子、古川亮、原島秀吉
    • Organizer
      日本核酸医薬学会 第1回年会
    • Place of Presentation
      京都テルサ(京都府京都市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] ミトコンドリア遺伝子発現DNAベクターの設計および遺伝子発現評価2015

    • Author(s)
      石川卓哉、山田勇磨、原島秀吉
    • Organizer
      日本核酸医薬学会 第1回年会
    • Place of Presentation
      京都テルサ(京都府京都市)
    • Year and Date
      2015-11-30
    • Related Report
      2015 Research-status Report
  • [Presentation] ミトコンドリア環境応答性核酸ナノ粒子の設計及びその評価2015

    • Author(s)
      福田豊、山田勇磨、原島秀吉
    • Organizer
      日本核酸医薬学会 第1回年会
    • Place of Presentation
      京都テルサ(京都府京都市)
    • Year and Date
      2015-11-30
    • Related Report
      2015 Research-status Report
  • [Presentation] MITO-Porter, an innovative technology for mitochondrial drug delivery2015

    • Author(s)
      Yuma Yamada
    • Organizer
      The 1st HU-TMU-KU Joint Symposium for Pharm. Sci.
    • Place of Presentation
      北海道大学(北海道札幌市)
    • Year and Date
      2015-08-29
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] MITO-Porter, mitochondrial drug delivery system toward innovative therapy2015

    • Author(s)
      Yuma Yamada, Hideyoshi Harashima
    • Organizer
      DRUG DELIVERY 2015, World Drug Delivery Summit
    • Place of Presentation
      Houston (USA)
    • Year and Date
      2015-08-18
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Targeted mitochondrial delivery of functional nucleic acids using MITO-Porter2015

    • Author(s)
      Eriko Kawamura, Yuma Yamada, Harashima Harashima
    • Organizer
      42nd Annual Meeting & Exposition of the Controlled Release Society
    • Place of Presentation
      Edinburgh (Scotland, UK)
    • Year and Date
      2015-07-28
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] ミトコンドリア標的型ナノマシン“MITO-Porter”の開発2015

    • Author(s)
      山田勇磨、原島秀吉
    • Organizer
      第24回日本Cell Death学会 シンポジウム1
    • Place of Presentation
      大阪大学会館(大阪府豊中市)
    • Year and Date
      2015-07-11
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] ミトコンドリアDDSが拓く医療・ライフサイエンス革命2015

    • Author(s)
      山田 勇磨
    • Organizer
      第31回日本DDS学会. 第7回奨励賞受賞講演
    • Place of Presentation
      京王プラザホテル(東京都新宿区)
    • Year and Date
      2015-07-03
    • Related Report
      2015 Research-status Report
    • Invited
  • [Book] “Pharmacology of Mitochondria” Handb Exp Pharmacol2017

    • Author(s)
      Yamada Y, Harashima H.
    • Publisher
      Springer
    • Related Report
      2016 Annual Research Report
  • [Book] Innovative Medicine2015

    • Author(s)
      Michitaka Ozaki, Takeaki Ozawa, Yuma Yamada
    • Total Pages
      339
    • Publisher
      Springer
    • Related Report
      2015 Research-status Report
  • [Remarks] 北海道大学 大学院薬学研究院 薬剤分子設計学研究室 HP

    • URL

      http://www.pharm.hokudai.ac.jp/yakusetu/

    • Related Report
      2016 Annual Research Report
  • [Remarks] 北海道大学 大学院薬学研究院 HP

    • URL

      http://www.pharm.hokudai.ac.jp/

    • Related Report
      2016 Annual Research Report
  • [Remarks] 平成28年度北海道科学技術賞・北海道科学技術奨励賞に関するHP

    • URL

      http://www.pref.hokkaido.lg.jp/kz/kgs/H28kagisyo_top.htm

    • Related Report
      2016 Annual Research Report
  • [Remarks] 7 SEAS PROJECT HP

    • URL

      https://7sp.life/

    • Related Report
      2016 Annual Research Report
  • [Remarks] 北海道大学 大学院薬学研究院 薬剤分子設計学研究室 HP

    • URL

      http://www.pharm.hokudai.ac.jp/

    • Related Report
      2015 Research-status Report
  • [Remarks] 北海道大学 大学院薬学研究院 HP

    • URL

      http://www.pharm.hokudai.ac.jp/yakusetu/

    • Related Report
      2015 Research-status Report
  • [Patent(Industrial Property Rights)] 心不全の治療及び/又は予防に用いるための心筋幹細胞2016

    • Inventor(s)
      原島秀吉, 山田勇磨, 阿部二郎、武田充人
    • Industrial Property Rights Holder
      国立大学法人 北海道大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2016-223069
    • Filing Date
      2016-11-16
    • Related Report
      2016 Annual Research Report

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Published: 2015-04-16   Modified: 2018-03-22  

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