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2019 年度 実績報告書

RNAアプタマーにより細胞種特異的翻訳活性化機能を付与したmRNA医薬品の開発

研究課題

研究課題/領域番号 18K19901
研究機関東京大学

研究代表者

Cabral Horacio  東京大学, 大学院工学系研究科(工学部), 准教授 (10533911)

研究分担者 内田 智士  東京大学, 大学院工学系研究科(工学部), 特任助教 (20710726)
研究期間 (年度) 2018-06-29 – 2020-03-31
キーワードmRNA / theophylline / polymer / protein translatiokn / aptamer
研究実績の概要

We developed mRNA-aptamer hybrids by combining mRNAs, and aptamers having a sequence for hybridization with mRNA and a binding site for theophylline. Then, PEG-theophylline conjugates were prepared by condensation. When the polymer was mixed with the mRNA-aptamer hybrids, it coated the hybrids, forming neutral nanoparticles of 50 nm in diameter. Conversely, mRNA-aptamer hybrids were negatively charged, which confirmed PEG coating. The nanoparticles were de-coated by adding free theophylline, recovering the negative charge. mRNA-aptamers translated proteins in cell free systems, and this translation was inhibited when coated with PEG-theophylline. After adding theophylline, protein translation was recovered, indicating that mRNA-aptamers-polymer nanoparticles can sense the surroundings.

  • 研究成果

    (17件)

すべて 2020 2019

すべて 雑誌論文 (9件) (うち国際共著 9件、 査読あり 9件、 オープンアクセス 1件) 学会発表 (8件) (うち国際学会 4件)

  • [雑誌論文] Enhanced MRI‐guided gadolinium (III) neutron capture therapy by polymeric nanocarriers promoting tumor accumulation and intracellular delivery.2020

    • 著者名/発表者名
      C. Qin, X. Hou, T. Khan, N. Nitta, M. Yanagawa, Y. Sakurai, M. Suzuki, S. Masunaga, H. Tanaka, Y. Sakurai, H. Takahashi, I. Aoki, H. Yanagie, H. Cabral
    • 雑誌名

      ChemNanoMat

      巻: - ページ: -

    • DOI

      10.1002/cnma.201900730

    • 査読あり / オープンアクセス / 国際共著
  • [雑誌論文] Nanomedicines blocking adaptive signals in cancer cells overcome tumor TKI resistance2020

    • 著者名/発表者名
      H. Kinoh, H. Shibasaki, X. Liu, T. Yamasoba, H. Cabral, K. Kataoka
    • 雑誌名

      J. Control. Release

      巻: 321 ページ: 132-144

    • DOI

      10.1016/j.jconrel.2020.02.008

    • 査読あり / 国際共著
  • [雑誌論文] Polymeric micelles loading proteins through concurrent ion complexation and pH-cleavable covalent bonding for in vivo delivery2020

    • 著者名/発表者名
      A. Tao, G. L. Huang, K. Igarashi, T. Hong, S. Liao, F. Stellacci, Y. Matsumoto, T. Yamasoba, K. Kataoka, H. Cabral
    • 雑誌名

      Macromol. Biosci.

      巻: 20 ページ: 1900161

    • DOI

      10.1002/mabi.201900161

    • 査読あり / 国際共著
  • [雑誌論文] Single-stranded DNA-packaged polyplex micelle as adeno-associated-virus-inspired compact vector to systemically target stroma-rich pancreatic cancer.2019

    • 著者名/発表者名
      T. A. Tockary, W. Foo, A. Dirisala, Q. Chen, S. Uchida, S. Osawa, Y. Mochida, X. Liu, H. Kinoh, H. Cabral, K. Osada, K. Kataoka
    • 雑誌名

      ACS Nano

      巻: 13 ページ: 12732-12742

    • DOI

      10.1021/acsnano.9b04676

    • 査読あり / 国際共著
  • [雑誌論文] One-pot synthesis of PEG-poly (amino acid) block copolymers assembling polymeric micelles with PEG-detachable functionality.2019

    • 著者名/発表者名
      T. Miyazaki, K. Igarashi, Y. Matsumoto, H. Cabral,
    • 雑誌名

      ACS Biomater. Sci. Eng.

      巻: 5 ページ: 5727-5733

    • DOI

      10.1021/acsbiomaterials.8b01549

    • 査読あり / 国際共著
  • [雑誌論文] Bundling mRNA strands to prepare nano-assemblies with enhanced stability towards RNase for in vivo delivery.2019

    • 著者名/発表者名
      N. Yoshinaga, E. Cho, K. Koji, Y. Mochida, M. Naito, K. Osada, K. Kataoka, H. Cabral, S. Uchida
    • 雑誌名

      Angew. Chem. Int. Ed.

      巻: 58 ページ: 11360-11363

    • DOI

      10.1002/anie.201905203

    • 査読あり / 国際共著
  • [雑誌論文] Dexamethasone increases cisplatin-loaded nanocarrier delivery and efficacy in metastatic breast cancer by normalizing the tumor microenvironment.2019

    • 著者名/発表者名
      J. Martin, M. Panagi, C. Wang, T. Khan, M. Martin, C. Voutouri, K. Toh, P. Papageorgis, F. Mpekris, C. Polydorou, G. Ishii, S. Takahashi, N. Gotohda, T. Suzuki, M. Wilhelm, V. Melo, S. Quader, J. Norimatsu, R. Lanning, M. Kojima, M. Stuber, T. Stylianopoulos, K. Kataoka, H. Cabral,
    • 雑誌名

      ACS Nano

      巻: 13 ページ: 6396-6408

    • DOI

      10.1021/acsnano.8b07865

    • 査読あり / 国際共著
  • [雑誌論文] PEG-oligoRNA hybridization of mRNA for developing sterically stable lipid nanoparticles toward in vivo administration.2019

    • 著者名/発表者名
      S. Kurimoto, N. Yoshinaga, K. Igarashi, Y. Matsumoto, H. Cabral, S. Uchida
    • 雑誌名

      Molecules

      巻: 24 ページ: 1303

    • DOI

      10.3390/molecules24071303

    • 査読あり / 国際共著
  • [雑誌論文] Induced packaging of mRNA into polyplex micelles by regulated hybridization with a small number of cholesteryl RNA oligonucleotides directed enhanced in vivo transfection.2019

    • 著者名/発表者名
      N. Yoshinaga, S. Uchida, M. Naito, K. Osada, H. Cabral, K. Kataoka,
    • 雑誌名

      Biomaterials

      巻: 197 ページ: 255-267

    • DOI

      10.1016/j.biomaterials.2019.01.023

    • 査読あり / 国際共著
  • [学会発表] Development of polymeric micelles with 5-Boronopicolinic acid ligand to target sialylated epitopes in intratumoral microenvironment"2019

    • 著者名/発表者名
      T. Khan, K. Igarashi, A. Matsumoto, H. Cabral, K. Kataoka
    • 学会等名
      32nd International Microprocesses and Nanotechnology Conference (MNC 2019)\
    • 国際学会
  • [学会発表] Mechanistic analyses of polymer/lipid-based gene transfection processes through membrane integrity assay using proton sensing transistor2019

    • 著者名/発表者名
      E. Boonstra, H. Hatano, T. Goda, S. Uchida, H. Cabral, Y. Miyahara
    • 学会等名
      4th International Symposium on Biomedical Engineering, ISBE 2019
    • 国際学会
  • [学会発表] nteraction analysis between target membrane proteins and ligand molecules attached to the polymeric micelle with different molecular weight of hydrophilic shell2019

    • 著者名/発表者名
      N.Nakamura, Y. Anraku, S. Fukushima, K. Tou, H. Cabral, K. Kataoka
    • 学会等名
      41st Annual Meeting of the Japanese Society for Biomaterials
    • 国際学会
  • [学会発表] Development of novel flexible block catiomers for forming stable polyion complex micelles with mRNA directed to in vivo applications2019

    • 著者名/発表者名
      W. Yang, T. Miyazaki, S. Uchida, H. Cabral
    • 学会等名
      2nd G'L'owing Polymer Symposium in Kanto
  • [学会発表] Development of pH-sensitive polymeric micelles effectively utilizing polymer freeze drying by liquid nitrogen2019

    • 著者名/発表者名
      Y. Tachihara, Y. Nakagawa, Y. Anraku, K. Kataoka, H. Cabral
    • 学会等名
      10th Research Meeting of Cryogenic Research Center
  • [学会発表] 薬剤送達システムへの応用を指向したホストゲスト相互作用による高分子-環状薬剤複合体の構築2019

    • 著者名/発表者名
      Y. Tachihara, Y. Nakagawa, Y. Anraku, K. Kataoka, H. Cabral
    • 学会等名
      Future Trend in Polymer Science 2018,
  • [学会発表] Development of pH-Sensitive Polymeric Micelles for Targeted Delivery of the Macrocycle Valinomycin via Host Guest Interaction2019

    • 著者名/発表者名
      Y. Tachihara, Y. Nakagawa, Y. Anraku, K. Kataoka, H. Cabral
    • 学会等名
      68th SPSJ Annual Meeting
    • 国際学会
  • [学会発表] Development of Macrocyclic Drug-Loaded pH-Sensitive Polymeric Micelles by Using Host Guest Interaction2019

    • 著者名/発表者名
      Y. Tachihara, Y. Nakagawa, Y. Anraku, K. Kataoka, H. Cabral
    • 学会等名
      TEJIN MIRAI FORUM 2020

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公開日: 2021-01-27  

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