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Construction of nucleic acid delivery carrier using biodegradable block copolymers

Research Project

Project/Area Number 18K18391
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 90120:Biomaterials-related
Research InstitutionKawasaki Institute of Industrial Promotion Innovation Center of NanoMedicine

Principal Investigator

Hayashi Kotaro  公益財団法人川崎市産業振興財団(ナノ医療イノベーションセンター), ナノ医療イノベーションセンター, 研究員 (00780660)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywordsバイオマテリアル / 機能性高分子 / 核酸デリバリー / 核酸医薬
Outline of Final Research Achievements

Delivery systems of antisense oligonucleotides (ASOs) are expected to expand the therapeutic application of ASO medicines. To overcome the first hurdle of delivery, that is the high stability under biological environment, triblock-copolymer for ASO micelle was designed to incorporate two protective layers, hydrophilic layer and hydrophobic layer. I developed a novel poly(amino acid) based thermo-responsible polymer. Synthesized poly(amino acid) polymer exhibited a phase transition around 31 degree and a sharp transition in response to pH around neutral. I have succeeded in n synthesizing ternary polymers incorporating this dual-environment-responsive polymer toward nanomicelles formation. This polymer was expected as biocompatible materials for highly-functionalized delivery carrier design for effective accumulation into target tissues.

Academic Significance and Societal Importance of the Research Achievements

アンチセンス核酸は難治性疾患に対して、疾病の原因遺伝子のmRNAを選択的に効率よく抑制、また、病因を引き起こすスプライシング異常を改善することから、次世代の分子標的薬として期待されているが、治療応用を加速していくために標的組織や細胞への送達効率を高める技術の確立が求められている。本研究では、送達技術の第一の課題である生体内での安定性の向上を狙い、疎水層として温度応答性セグメントを組み込んだ二重保護化ミセル型ナノ粒子の開発を目的としている。また、温度応答性セグメントとカチオンにポリアミノ酸ベースの高分子を用いることで、生体内で分解性を付与し、より臨床応用を指向したデザインとなることが期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (14 results)

All 2020 2019 2018

All Journal Article (4 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 4 results,  Open Access: 1 results) Presentation (7 results) Patent(Industrial Property Rights) (3 results) (of which Overseas: 3 results)

  • [Journal Article] In vivo rendezvous of small nucleic acid drugs with charge-matched block catiomers to target cancers2019

    • Author(s)
      Watanabe Sumiyo、Hayashi Kotaro、Toh Kazuko、Kim Hyun Jin、Liu Xueying、Chaya Hiroyuki、Fukushima Shigeto、Katsushima Keisuke、Kondo Yutaka、Uchida Satoshi、Ogura Satomi、Nomoto Takahiro、et al.
    • Journal Title

      Nature Communications

      Volume: 10 Issue: 1 Pages: 1894-1894

    • DOI

      10.1038/s41467-019-09856-w

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dually stabilized triblock copolymer micelles with hydrophilic shell and hydrophobic interlayer for systemic antisense oligonucleotide delivery to solid tumor2019

    • Author(s)
      Beob Soo Kim, Hyun Jin Kim, Shigeto Osawa, Kotaro Hayashi, Kazuko Toh, Mitsuru Naito, Hyun Su Min, Yu Yi, Ick Chan Kwon, Kazunori Kataoka, Kanjiro Miyata
    • Journal Title

      ACS Biomaterials Science & Engineering

      Volume: 5 Issue: 11 Pages: 5770-5780

    • DOI

      10.1021/acsbiomaterials.9b00384

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Glucose-linked sub-50-nm unimer polyion complex-assembled gold nanoparticles for targeted siRNA delivery to glucose transporter 1-overexpressing breast cancer stem-like cells.2019

    • Author(s)
      Y. Yi, H. J. Kim, M. Zheng, P. Mi, M. Naito, B. S. Kim, H. S. Min, K. Hayashi, F. Perche, K. Toh, X. Liu, Y. Mochida, H. Kinoh, H. Cabral, K. Miyata, K. Kataoka
    • Journal Title

      J. Control. Release

      Volume: 295 Pages: 268-277

    • DOI

      10.1016/j.jconrel.2019.01.006

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Self-Assembly of siRNA/PEG-b-Catiomer at Integer Molar Ratio into 100 nm-Sized Vesicular Polyion Complexes (siRNAsomes) for RNAi and Codelivery of Cargo Macromolecules2019

    • Author(s)
      Kim Beob Soo、Chuanoi Sayan、Suma Tomoya、Anraku Yasutaka、Hayashi Kotaro、Naito Mitsuru、Kim Hyun Jin、Kwon Ick Chan、Miyata Kanjiro、Kishimura Akihiro、Kataoka Kazunori
    • Journal Title

      Journal of the American Chemical Society

      Volume: 141 Issue: 8 Pages: 3699-3709

    • DOI

      10.1021/jacs.8b13641

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] ポリアミノ酸骨格を有する温度応答性ポリマーの合成と機能評価2019

    • Author(s)
      林光太朗、片岡一則
    • Organizer
      第68回高分子学会年次大会
    • Related Report
      2019 Research-status Report
  • [Presentation] カチオン性ブロック共重合体の重合度がsiRNA会合体の構造に与える効果2019

    • Author(s)
      林光太朗、福島重人、長田健介、西山伸宏、宮田完二郎、片岡一則
    • Organizer
      第29回バイオ高分子シンポジウム
    • Related Report
      2019 Research-status Report
  • [Presentation] siRNA 送達に向けたカチオン性ポリアミノ酸の検討2019

    • Author(s)
      林光太朗、福島重人、西山伸宏、宮田完二郎、片岡一則
    • Organizer
      第68回高分子学会討論会
    • Related Report
      2019 Research-status Report
  • [Presentation] ポリアミノ酸骨格を有する温度応答性ポリマーの合成と機能評価2019

    • Author(s)
      林光太朗 ・片岡一則
    • Organizer
      第68回高分子学会年次大会
    • Related Report
      2018 Research-status Report
  • [Presentation] ナノメディシンへの展開に向けた siRNA とブロック共重合体からなる最小単位の会合体形成2018

    • Author(s)
      林光太朗 ・福島重人 ・長田健介 ・西山伸宏 ・宮田完二郎 ・片岡一則
    • Organizer
      第67回高分子学会年次大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 核酸医薬の送達に向けた RNA とブロック共重合体の会合の物理化学的解析2018

    • Author(s)
      林光太朗 ・福島重人 ・長田健介 ・西山伸宏 ・宮田完二郎 ・片岡一則
    • Organizer
      第28回バイオ・高分子シンポジウム
    • Related Report
      2018 Research-status Report
  • [Presentation] siRNA 送達に向けたカチオン性ポリアミノ酸の検討2018

    • Author(s)
      林光太朗 ・福島重人 ・西山伸宏 ・宮田完二郎 ・片岡一則
    • Organizer
      第67回高分子学会討論会
    • Related Report
      2018 Research-status Report
  • [Patent(Industrial Property Rights)] 刺激応答性ポリマー2020

    • Inventor(s)
      林光太朗、片岡一則
    • Industrial Property Rights Holder
      川崎市産業振興財団
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2020 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 刺激応答性ポリマー2019

    • Inventor(s)
      林光太郎、片岡一則
    • Industrial Property Rights Holder
      川崎市産業振興財団
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2019 Research-status Report
    • Overseas
  • [Patent(Industrial Property Rights)] 刺激応答性ポリマー2019

    • Inventor(s)
      林光太朗・片岡一則
    • Industrial Property Rights Holder
      川崎市産業振興財団
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2018 Research-status Report
    • Overseas

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Published: 2018-04-23   Modified: 2022-01-27  

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