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Development of mRNA medicine for treatment of neural diseases and injury

Research Project

Project/Area Number 15H03017
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biomedical engineering/Biomaterial science and engineering
Research InstitutionTokyo Medical and Dental University (2017-2018)
The University of Tokyo (2015-2016)

Principal Investigator

ITAKA Keiji  東京医科歯科大学, 生体材料工学研究所, 教授 (60292926)

Co-Investigator(Kenkyū-buntansha) 緒方 徹  国立障害者リハビリテーションセンター(研究所), 病院 障害者健康増進・運動医科学支援センター(研究所併任), 障害者健康増進・運動医科学支援センター長 (00392192)
小牧 裕司  公益財団法人実験動物中央研究所, ライブイメージングセンター, 室長代理 (10548499)
筑田 博隆  群馬大学, 大学院医学系研究科, 教授 (30345219)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2017: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
KeywordsmRNA / 送達システム / 神経疾患 / 脊髄損傷 / mRNA医薬 / DDS / 難治神経疾患
Outline of Final Research Achievements

mRNA medicine is a new type nucleic acid medicine, by administering mRNA directly into the body. In this study, we evaluated the feasibility of mRNA medicine for treatment of neural diseases and injury. The study was done by optimization of mRNA molecule structure and its DDS, and the evaluation of the therapeutic effects using model animals of neural diseases and injury. The effects of mRNA medicine were obtained in the animal models of Alzheimer disease and spinal cord injury.

Academic Significance and Societal Importance of the Research Achievements

mRNA医薬は世界的に研究開発が活発化しており、近い将来の実用化が期待される。従来と異なる作用機序により、多くの難治疾患治療や再生医療への応用が研究されている。本研究は特に神経疾患外傷へのmRNA医薬応用に関わる先駆的な研究と位置づけられ、脳におけるmRNA投与による治療効果など、世界で初めての成果も得られている。今後さらに治療効果や安全性についての検証が進められ、我が国発のmRNA医薬実用化に繋がることが期待される。

Report

(4 results)
  • 2018 Final Research Report ( PDF )
  • 2017 Annual Research Report
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (43 results)

All 2019 2018 2016 2015 Other

All Journal Article (16 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 12 results,  Open Access: 8 results,  Acknowledgement Compliant: 5 results) Presentation (23 results) (of which Int'l Joint Research: 11 results,  Invited: 17 results) Remarks (3 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] mRNA医薬の研究開発動向と将来展望2019

    • Author(s)
      位髙啓史
    • Journal Title

      医薬ジャーナル

      Volume: 55 Pages: 627-632

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Treatment of intervertebral disk disease by administration of messenger RNA encoding a cartilage-anabolic transcription factor.2019

    • Author(s)
      C. -Y. Lin, S. T. Crowley, S. Uchida, Y. Komaki, K. Kataoka, K. Itaka
    • Journal Title

      Mol. Ther. Nucleic Acids

      Volume: 16 Pages: 162-171

    • DOI

      10.1016/j.omtn.2019.02.012

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Combined CatWalk Index: an improved method to measure mouse motor function using the automated gait analysis system2018

    • Author(s)
      Crowley S, Kataoka K, Itaka K
    • Journal Title

      BMC Research Notes

      Volume: 11 Issue: 1 Pages: 263-263

    • DOI

      10.1186/s13104-018-3374-x

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Prolonged engraftment of transplanted hepatocytes in the liver by transient pro-survival factor supplementation using ex vivo mRNA transfection.2018

    • Author(s)
      A. Matsui, S. Uchida, A. Hayashi, K. Kataoka, K. Itaka
    • Journal Title

      J. Control. Release

      Volume: 285 Pages: 1-11

    • DOI

      10.1016/j.jconrel.2018.06.033

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] mRNA医薬を用いた脳神経疾患の治療戦略2018

    • Author(s)
      位髙啓史、福島雄大
    • Journal Title

      バイオマテリアル-生体材料-

      Volume: 36 Pages: 220-223

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Messenger RNA-based therapeutics for brain diseases: An animal study for augmenting clearance of beta-amyloid by intracerebral administration of neprilysin mRNA loaded in polyplex nanomicelles2016

    • Author(s)
      Lin CY, Perche F, Ikegami M, Uchida S, Kataoka K, Itaka K
    • Journal Title

      J Control Release

      Volume: 235 Pages: 268-275

    • DOI

      10.1016/j.jconrel.2016.06.001

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Treatment of spinal cord injury by an advanced cell transplantation technology using brain-derived neurotrophic factor-transfected mesenchymal stem cell spheroids2016

    • Author(s)
      Uchida S, Hayakawa K, Ogata T, Tanaka S, Kataoka K, Itaka K
    • Journal Title

      Biomaterials

      Volume: 109 Pages: 1-11

    • DOI

      10.1016/j.biomaterials.2016.09.007

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Development of mRNA-based therapeutics2016

    • Author(s)
      Itaka K
    • Journal Title

      Nihon Yakurigaku Zasshi

      Volume: 148 Pages: 190-196

    • NAID

      130005598209

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] メッセンジャーRNA医薬を実現するDDS開発と疾患治療への応用2016

    • Author(s)
      位髙啓史
    • Journal Title

      Drug Delivery System (DDS)

      Volume: 31 Pages: 343-351

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Screening of mRNA chemical modification to maximize protein expression with reduced immunogenicity.2016

    • Author(s)
      S. Uchida, K. Kataoka, K. Itaka
    • Journal Title

      Pharmaceutics

      Volume: 7 Issue: 3 Pages: 137-151

    • DOI

      10.3390/pharmaceutics7030137

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Messenger RNA delivery of a cartilage-anabolic transcription factor as a disease-modifying strategy for osteoarthritis treatment.2016

    • Author(s)
      1.Aini H, Itaka K, Fujisawa A, Uchida H, Uchida S, Fukushima S, Kataoka K, Saito T, Chung UI, Ohba S.
    • Journal Title

      Sci Rep.

      Volume: 6 Issue: 1 Pages: 18743-18743

    • DOI

      10.1038/srep18743

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Systemic delivery of messenger RNA for the treatment of pancreatic cancer using polyplex nanomicelles with a cholesterol moiety.2016

    • Author(s)
      S. Uchida, H. Kinoh, T. Ishii, A. Matsui, T. A. Tockary, K. M. Takeda, H. Uchida, K. Osada, K. Itaka, K. Kataoka
    • Journal Title

      Biomaterials

      Volume: 82 Pages: 221-228

    • DOI

      10.1016/j.biomaterials.2015.12.031

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Synthetic polyamines to regulate mRNA translation through the preservative binding of eukaryotic initiation factor 4E to the cap structure.2016

    • Author(s)
      H. Uchida, K. Itaka, S. Uchida, T. Ishii, T. Suma, K. Miyata, M. Oba, N. Nishiyama, K. Kataoka
    • Journal Title

      J. Am. Chem. Soc.

      Volume: 138 Issue: 5 Pages: 1478-1481

    • DOI

      10.1021/jacs.5b11726

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Introduction to Special Issue: A New Paradigm of Gene Therapy2016

    • Author(s)
      Itaka K
    • Journal Title

      Pharmaceutics

      Volume: 8 Issue: 1 Pages: 1-1

    • DOI

      10.3390/pharmaceutics8010001

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Messenger RNA-based therapeutics for the treatment of apoptosis-associated diseases.2015

    • Author(s)
      A. Matsui, S. Uchida, T. Ishii, K. Itaka, K. Kataoka
    • Journal Title

      Scientific Reports

      Volume: 5 Issue: 1 Pages: 15810-15810

    • DOI

      10.1038/srep15810

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] ナノDDSの再生医療への展開:mRNAデリバリーによる生体内細胞制御2015

    • Author(s)
      位髙啓史,片岡一則
    • Journal Title

      細胞工学

      Volume: 34 Pages: 946-951

    • Related Report
      2015 Annual Research Report
  • [Presentation] Enhancement of motor function recovery in mice by delivery of mRNA nanomicelles encoding brain derived neurotrophic factor2018

    • Author(s)
      Samuel Crowley, Kazunori Kataoka, Keiji Itaka
    • Organizer
      3rd Japan-US Technical Information Exchange Forum on Blast Injury
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] mRNA-based therapy for intractable diseases and regenerative medicine2018

    • Author(s)
      Keiji Itaka
    • Organizer
      The 6th Japan-China Symposium on Nanomedicine
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Treatment of spinal cord injury by injection of therapeutic mRNA-containing nanomicelles2018

    • Author(s)
      Samuel Crowley, 内田智士、片岡一則、位髙啓史
    • Organizer
      第34回日本DDS学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] mRNA医薬の研究開発動向2018

    • Author(s)
      位髙啓史
    • Organizer
      日本核酸医薬学会第4回年会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] mRNA-based therapy for cartilage degeneration diseases2018

    • Author(s)
      Keiji Itaka, Shinsuke Ohba, Satoshi Uchida, Ung-il Chung, Kazunori Kataoka
    • Organizer
      5th TERMIS World Congress
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] mRNAが生み出すパラダイムシフト~新たな核酸医薬品開発に向けて~2018

    • Author(s)
      位髙啓史
    • Organizer
      第24回創剤フォーラム若手研究会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] mRNA医薬を用いた脳神経疾患治療2018

    • Author(s)
      位髙啓史
    • Organizer
      第37回日本認知症学会学術集会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] mRNA-based therapy for intractable diseases and regenerative medicine2018

    • Author(s)
      Keiji Itaka
    • Organizer
      3rd International Symposium on Biomedical Engineering
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] mRNA medicine as a new paradigm of gene therapy for intractable diseases and regenerative medicine2018

    • Author(s)
      Keiji Itaka
    • Organizer
      6th International mRNA Health Conference
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] mRNA delivery using nano drug delivery systems for intractable diseases and regenerative medicine2016

    • Author(s)
      Keiji Itaka
    • Organizer
      Emerging Therapeutics Summit (ETS’16)
    • Place of Presentation
      Melbourne,Australia
    • Year and Date
      2016-11-25
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] An Animal Study for Augmenting Clearance of Beta-Amyloid Using Neprilysin mRNA2016

    • Author(s)
      Keiji Itaka, Chin-Yu Lin, Satoshi Uchida, Kazunori Kataoka
    • Organizer
      4th International mRNA Conference
    • Place of Presentation
      Boston, MA, USA
    • Year and Date
      2016-11-01
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] mRNA医薬品の開発と治療応用に向けた戦略2016

    • Author(s)
      位髙啓史
    • Organizer
      日本薬物動態学会第31回会年会
    • Place of Presentation
      キッセイ文化ホール(長野県松本市)
    • Year and Date
      2016-10-15
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] メッセンジャーRNA医薬を実現するDDS開発と疾患治療への応用2016

    • Author(s)
      位髙啓史
    • Organizer
      第32回日本DDS学会学術集会
    • Place of Presentation
      静岡県コンベンションアーツセンター(静岡県静岡市)
    • Year and Date
      2016-07-01
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] mRNA delivery using nano drug delivery systems for intractable diseases and regenerative medicine2016

    • Author(s)
      Keiji Itaka
    • Organizer
      Ireland-Japan Biomaterials & Tissue Engineering Meeting
    • Place of Presentation
      Galway, Ireland
    • Year and Date
      2016-06-23
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] mRNA-based therapeutics using nanoDDS for intractable diseases and serious injury2016

    • Author(s)
      Keiji Itaka
    • Organizer
      Japan-US Forum on Blast Injury 2016
    • Place of Presentation
      ニュー山王ホテル(東京都港区)
    • Year and Date
      2016-06-14
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ナノDDSを用いたmRNAデリバリーとその応用2016

    • Author(s)
      位髙啓史
    • Organizer
      第63回日本実験動物学会総会
    • Place of Presentation
      ミューザ川崎シンフォニーホール(神奈川県川崎市)
    • Year and Date
      2016-05-19
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 新しいバイオ医薬品としてのメッセンジャーRNAの可能性2016

    • Author(s)
      位髙啓史
    • Organizer
      第15回国際バイオテクノロジー展(BIOTech2016)
    • Place of Presentation
      東京ビッグサイト(東京都江東区)
    • Year and Date
      2016-05-13
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 転写因子mRNAの関節内投与による変形性関節症治療2015

    • Author(s)
      位髙啓史,Hailati Aini, 内田寛邦,内田智士,鄭雄一,大庭伸介,片岡一則
    • 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 Annual Research Report
  • [Presentation] A disease-modifying strategy for osteoarthritis treatment by introducing mRNA encoding cartilage-anabolic transcription factor2015

    • Author(s)
      Keiji Itaka,Hailati Aini, Shinsuke Ohba, Ung-il Chung, Kazunori Kataoka.
    • Organizer
      3rd International mRNA Health Conference
    • Place of Presentation
      Berlin, Germany
    • Year and Date
      2015-11-14
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] メッセンジャーRNAデリバリーによる運動感覚機能再建2015

    • Author(s)
      位髙啓史,片岡一則
    • Organizer
      日本化学会,第5回CSJ化学フェスタ2015
    • Place of Presentation
      タワーホール船堀(東京都江戸川区)
    • Year and Date
      2015-10-13
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 新しいバイオ医薬品としてのmRNA2015

    • Author(s)
      位髙啓史
    • Organizer
      GE Life Sciences Day 2015
    • Place of Presentation
      パシフィコ横浜会議センター(神奈川県横浜市)
    • Year and Date
      2015-07-24
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] メッセンジャーRNAを用いた新しい遺伝子治療と再生医療への応用2015

    • Author(s)
      位髙啓史,内田智士,片岡一則
    • Organizer
      第31回日本DDS学会学術集会
    • 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 Annual Research Report
    • Invited
  • [Presentation] Treating neurological disorders by in vivo mRNA introduction using polyplex nanomicelles2015

    • Author(s)
      Keiji Itaka, Miyuki Baba, Hirokuni Uchida, Satoshi Uchida, Kazunori Kataoka
    • Organizer
      Biomaterials International 2015
    • Place of Presentation
      Kenting,Taiwan
    • Year and Date
      2015-06-04
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Remarks] 東京医科歯科大学生体材料工学研究所 生体材料機能医学分野

    • URL

      http://www.tmd.ac.jp/i-mde/www/biofunctions/biofunctions-j.html

    • Related Report
      2017 Annual Research Report
  • [Remarks] 東京医科歯科大学生体材料工学研究所

    • URL

      http://www.tmd.ac.jp/i-mde/www/index.html

    • Related Report
      2016 Annual Research Report
  • [Remarks] 東京大学 片岡研究室

    • URL

      http://www.bmw.t.u-tokyo.ac.jp/member/itaka.html

    • Related Report
      2015 Annual Research Report
  • [Patent(Industrial Property Rights)] mRNAを効率よく生体内に送達できるポリイオンコンプレックス並びにこれを用いた関節症の治療薬および治療法2015

    • Inventor(s)
      位髙啓史,大庭伸介,鄭雄一,片岡一則
    • Industrial Property Rights Holder
      位髙啓史
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2015-151564
    • Filing Date
      2015-07-31
    • Related Report
      2015 Annual Research Report

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Published: 2015-04-16   Modified: 2020-03-30  

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