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In vivo suppression of apoptosis signaling using mRNA therapeutics for the treatment of ischemic diseases

Research Project

Project/Area Number 15K20962
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Biomedical engineering/Biomaterial science and engineering
Applied pharmacology
Research InstitutionThe University of Tokyo

Principal Investigator

Uchida Satoshi  東京大学, 大学院工学系研究科(工学部), 特任助教 (20710726)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsmRNA医薬 / 高分子ミセル / 遺伝子治療 / アポトーシス / 虚血性疾患 / mRNA導入 / 下肢虚血性疾患 / ナノミセル / mRNAデリバリー / 抗アポトーシス因子
Outline of Final Research Achievements

Introduction of pro-survival gene is an attractive strategy for treatment of ischemic diseases, and mRNA therapeutics is a safe and promising methodology for this purpose. While mRNA is subjected to nuclease degradation soon after in vivo delivery, we successfully solved this issue by encapsulating mRNA into biocompatible polyplex micelles. Then, we attempted treatment of hind limb ischemia by delivering mRNA encoding myr-Akt, a pro-survival factor, using polyplex micelles. The treatment resulted in significant recovery of blood flow in mouse hind limb. The mRNA-based pro-survival factor introduction is a promising strategy for the treatment of various diseases accompanying enhanced cell death, including ischemic diseases.

Report

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

    (35 results)

All 2018 2017 2016 2015 Other

All Int'l Joint Research (1 results) Journal Article (16 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 16 results,  Open Access: 7 results,  Acknowledgement Compliant: 6 results) Presentation (10 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results) Book (1 results) Remarks (1 results) Patent(Industrial Property Rights) (6 results) (of which Overseas: 2 results)

  • [Int'l Joint Research] ルートヴィヒ・マクシミリアン大学ミュンヘン(ドイツ)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] Designing immunostimulatory double stranded messenger RNA with maintained translational activity through hybridization with poly A sequences for effective vaccination2018

    • Author(s)
      Uchida Satoshi、Yoshinaga Naoto、Yanagihara Kayoko、Yuba Eiji、Kataoka Kazunori、Itaka Keiji
    • Journal Title

      Biomaterials

      Volume: 150 Pages: 162-170

    • DOI

      10.1016/j.biomaterials.2017.09.033

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Polyplex Micelles with Phenylboronate/Gluconamide Cross-Linking in the Core Exerting Promoted Gene Transfection through Spatiotemporal Responsivity to Intracellular pH and ATP Concentration2017

    • Author(s)
      Yoshinaga Naoto、Ishii Takehiko、Naito Mitsuru、Endo Taisuke、Uchida Satoshi、Cabral Horacio、Osada Kensuke、Kataoka Kazunori
    • Journal Title

      Journal of the American Chemical Society

      Volume: 139 Issue: 51 Pages: 18567-18575

    • DOI

      10.1021/jacs.7b08816

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Glycaemic control boosts glucosylated nanocarrier crossing the BBB into the brain2017

    • Author(s)
      Anraku Y.、Kuwahara H.、Fukusato Y.、Mizoguchi A.、Ishii T.、Nitta K.、Matsumoto Y.、Toh K.、Miyata K.、Uchida S.、Nishina K.、Osada K.、Itaka K.、Nishiyama N.、Mizusawa H.、Yamasoba T.、Yokota T.、Kataoka K.
    • Journal Title

      Nat Commun

      Volume: 8 Issue: 1 Pages: 2001-2009

    • DOI

      10.1038/s41467-017-00952-3

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Systemic Delivery of Folate-PEG siRNA Lipopolyplexes with Enhanced Intracellular Stability for In Vivo Gene Silencing in Leukemia2017

    • Author(s)
      Lee Dian-Jang、Kessel Eva、Lehto Taavi、Liu Xueying、Yoshinaga Naoto、Padari K?rt、Chen Ying-Chen、Kempter Susanne、Uchida Satoshi、R?dler Joachim O.、Pooga Margus、Sheu Ming-Thau、Kataoka Kazunori、Wagner Ernst
    • Journal Title

      Bioconjugate chemistry

      Volume: 28 Issue: 9 Pages: 2393-2409

    • DOI

      10.1021/acs.bioconjchem.7b00383

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Improved brain expression of anti-amyloid β scFv by complexation of mRNA including a secretion sequence with PEG-based block catiomer.2017

    • Author(s)
      F. Perche, S. Uchida, H. Akiba, C.-Y. Lin, M. Ikegami, A. Disrala, T. Nakashima, K. Itaka, K. Tsumoto, K. Kataoka
    • Journal Title

      Curr. Alzheimer Res.

      Volume: 14 Issue: 3 Pages: 295-302

    • DOI

      10.2174/1567205013666161108110031

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Polyplex micelle installing intracellular self-processing functionalities without free catiomers for safe and efficient systemic gene therapy through tumor vasculature targeting2016

    • Author(s)
      Q. Chen, K. Osada, Z. Ge, S. Uchida, T. A. Tockary, A. Dirisala, A. Matsui, K. Toh, K. M. Takeda, X. Liu, T. Nomoto, T. Ishii, M. Oba, Y. Matsumoto, K. Kataoka
    • Journal Title

      Biomaterials

      Volume: 113 Pages: 253-265

    • DOI

      10.1016/j.biomaterials.2016.10.042

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [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 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [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 Research-status 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 Research-status Report
    • Peer Reviewed / Open Access
  • [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 Research-status Report
    • Peer Reviewed / 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 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [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 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [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 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Toroidal packaging of pDNA into block ionomer micelles exerting promoted in vivo gene expression.2015

    • Author(s)
      Y. Li, K. Osada, Q. Chen, T. A. Tockary, A. Dirisala, K. M. Takeda, S. Uchida, K. Nagata, K. Itaka, K. Kataoka
    • Journal Title

      Biomacromolecules

      Volume: 16 Issue: 9 Pages: 2664-2671

    • DOI

      10.1021/acs.biomac.5b00491

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of biodegradable polycation-based inhalable dry gene powders by spray freeze drying.2015

    • Author(s)
      T. Okuda, Y. Suzuki, Y. Kobayashi, T. Ishii, S. Uchida, K. Itaka, K. Kataoka, H. Okamoto
    • Journal Title

      Pharmaceutics

      Volume: 7 Issue: 3 Pages: 233-254

    • DOI

      10.3390/pharmaceutics7030233

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Gene transfection toward spheroid cells on micropatterned culture plates for genetically-modified cell transplantation.2015

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

      Journal of Visualized Experiments

      Volume: 101 Issue: 101

    • DOI

      10.3791/52384

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] 高分子ミセルを用いたメッセンジャーRNAデリバリー2017

    • Author(s)
      内田智士
    • Organizer
      理研シンポジウム:理研/iCONM/物材研 医工学ネットワーク
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 免疫賦活化能を向上させた2本鎖メッセンジャーRNAワクチンの開発2017

    • Author(s)
      内田 智士、吉永 直人、柳原 歌代子、弓場 獎司、位髙 啓史、片岡 一則
    • Organizer
      第39回日本バイオマテリアル学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] mRNA搭載ナノミセルを用いた抗アミロイドβ単鎖抗体導入によるアルツハイマー病治療2017

    • Author(s)
      内田 智士、F. Perche、秋葉 宏樹、位髙 啓史、津本 浩平、片岡 一則
    • Organizer
      日本核酸医薬学会第3回年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 抗アミロイドβ単鎖抗体発現mRNA搭載ナノミセルを用いたアルツハイマー病治療2017

    • Author(s)
      内田 智士、F. Perche、秋葉 宏樹、位髙 啓史、津本 浩平、片岡 一則
    • Organizer
      第33回日本DDS学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Development of polyplex nanomicelles for systemic messenger RNA delivery targeting pancreatic cancer.2016

    • Author(s)
      S. Uchida, H. Kinoh, T. Ishii, A. Matsui, H. Uchida, K. Itaka, K. Kataoka.
    • Organizer
      Gorden Research Conference (Drug Carriers in Medicine & Biology)
    • Place of Presentation
      Waterville Valley, NH, USA
    • Year and Date
      2016-08-08
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] コレステロール修飾ナノミセルを用いたmRNA全身投与による膵臓がん治療2016

    • Author(s)
      内田智士、喜納宏昭、石井武彦、内田寛邦、松井秋倫、位髙啓史、片岡一則
    • Organizer
      第32回日本DDS学会学術集会
    • Place of Presentation
      静岡県 静岡市
    • Year and Date
      2016-06-30
    • Related Report
      2016 Research-status Report
  • [Presentation] Anti-angiogenic therapy for pancreatic cancer by systemic delivery of messenger RNA using polyplex nanomicelle.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
    • Organizer
      ASGCT 19th Annual Meeting
    • Place of Presentation
      Washington, DC, USA
    • Year and Date
      2016-05-06
    • Related Report
      2016 Research-status Report
  • [Presentation] mRNAの全身投与に向けた高分子ナノミセルの開発と膵臓がん治療への応用2015

    • Author(s)
      内田 智士、喜納 宏昭、石井 武彦、松井 秋倫、位髙 啓史、片岡 一則
    • Organizer
      第37回日本バイオマテリアル学会大会
    • Place of Presentation
      京都府京都市
    • Year and Date
      2015-11-09
    • Related Report
      2015 Research-status Report
  • [Presentation] Messenger RNA-based therapy for an apoptosis-related disease in the liver.2015

    • Author(s)
      S. Uchida, A. Matsui, K Kataoka, K. Itaka
    • Organizer
      ESGCT and FSGT Collaborative Congress
    • Place of Presentation
      Helsinki, Finland
    • Year and Date
      2015-09-18
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Messenger RNA (mRNA)-based gene therapy for introducing anti-apoptotic factor.2015

    • Author(s)
      S. Uchida, A. Matsui, K. Itaka, K Kataoka
    • Organizer
      American Society of Gene and Cell Therapy (ASGCT) 18th Annual Meeting
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2015-05-22
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Book] 高分子ナノミセルを用いた生体へのin vivo mRNAデリバリー トランスレーショナルリサーチを支援する遺伝子医学MOOK30号 今、着実に実り始めた遺伝子治療-最新研究と今後の展開2016

    • Author(s)
      内田智士,位高啓史,片岡一則
    • Total Pages
      300
    • Publisher
      株式会社メディカルドゥ
    • Related Report
      2016 Research-status Report
  • [Remarks] researchmap

    • URL

      https://researchmap.jp/suchida

    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] mRNAの機能化方法2017

    • Inventor(s)
      内田智士、吉永直人、位髙啓史、片岡一則
    • Industrial Property Rights Holder
      東京大学、川崎市産業振興財団
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Related Report
      2017 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] METHOD FOR STABILIZING MRNA2017

    • Inventor(s)
      内田智士、吉永直人、趙オル
    • Industrial Property Rights Holder
      東京大学、川崎市産業振興財団
    • Industrial Property Rights Type
      特許
    • Filing Date
      2017
    • Related Report
      2017 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 体内における薬物動態を制御する組成物2017

    • Inventor(s)
      片岡一則、大澤重仁、内田智士、林光太郎、藤加珠子、ディリサラ
    • Industrial Property Rights Holder
      川崎市産業振興財団
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-195061
    • Filing Date
      2017
    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] 血中におけるRNAの安定性の改善剤および投与方法2017

    • Inventor(s)
      片岡一則、大澤重仁、林光太郎、内田智士、長田健介
    • Industrial Property Rights Holder
      川崎市産業振興財団
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2017-104975
    • Filing Date
      2017
    • Related Report
      2017 Annual Research Report
  • [Patent(Industrial Property Rights)] mRNA輸送担体の安定化方法2016

    • Inventor(s)
      内田 智士,片岡 一則,吉永 直人,位高 啓史
    • Industrial Property Rights Holder
      東京大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2016-252488
    • Filing Date
      2016-12-27
    • Related Report
      2016 Research-status Report
  • [Patent(Industrial Property Rights)] mRNAワクチン2016

    • Inventor(s)
      内田 智士,位高 啓史,片岡 一則
    • Industrial Property Rights Holder
      東京大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2016-252487
    • Filing Date
      2016-12-27
    • Related Report
      2016 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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