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Novel targeting system of circulating non-coding RNAs for the inhibition of cancer metastasis

Research Project

Project/Area Number 18H02087
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 37010:Bio-related chemistry
Research InstitutionNagasaki University

Principal Investigator

YAMAYOSHI Asako  長崎大学, 医歯薬学総合研究科(薬学系), 教授 (70380532)

Co-Investigator(Kenkyū-buntansha) 芦原 英司  京都薬科大学, 薬学部, 教授 (70275197)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2019: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
Keywordsエクソソーム / microRNA / 核酸医薬 / 抗体結合型核酸 / non-coding RNA / 抗体 / ハイジャック / anti-miR / DDS / 癌 / 転移
Outline of Final Research Achievements

MicroRNAs in exosomes (exosomal miRNAs) are considered as significant targets for cancer therapy. AntimiR oligonucleotides are often used for the functional inhibition of miRNA; however, there are no studies regarding the regulation of exosomal miRNA functions. In this study, we attempted to develop a novel drug delivery system using anti-exosome antibody-antimiR oligonucleotide complexes (ExomiR-Tracker) to hijack exosomes to carry AntimiR oligonucleotides inside exosome-recipient cells. We found that ExomiR-Tracker bound to the exosomes, and then, the complexes were introduced into the recipient cells. We also found that Anti-miR oligonucleotides introduced into the recipient cells can exhibit inhibitory effects on exosomal-miRNA functions in vitro and in vivo. We believe that our strategy would be a promising one for targeting exosomal-miRNAs.

Academic Significance and Societal Importance of the Research Achievements

我々は、極微量で高度な機能を発揮し、生体制御系に大きな役割を果たしているexosomal-miRNAを標的とした機能性分子の開発に成功した。近年、エクソソームを回収した後、様々な分子を内包させることでDDSとして利用する研究が盛んに行われているが、 我々の開発した手法はエクソソームを単離・精製する必要がなく、体内に直接投与できるという点において一線を画すものである。このExomiR-Trackerは、anti-miR核酸だけでなく、mRNAを標的としたアンチセンス核酸、siRNA、アプタマー、さらには核酸だけでなく低分子化合物を搭載することも可能である。

Report

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

    (47 results)

All 2021 2020 2019 2018 Other

All Journal Article (8 results) (of which Peer Reviewed: 7 results,  Open Access: 2 results) Presentation (34 results) (of which Int'l Joint Research: 9 results,  Invited: 14 results) Book (2 results) Remarks (3 results)

  • [Journal Article] エクソソーム表面抗原に着目した新たな創薬モダリティの探索2021

    • Author(s)
      大山将大、山吉麻子
    • Journal Title

      Drug Delivery System

      Volume: 36 Pages: 108-116

    • NAID

      130008056983

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Development of Novel Drug Delivery System Targeting Exosomal microRNA2020

    • Author(s)
      Yamayoshi Asako
    • Journal Title

      YAKUGAKU ZASSHI

      Volume: 140 Issue: 5 Pages: 625-631

    • DOI

      10.1248/yakushi.19-00218-3

    • NAID

      130007838708

    • ISSN
      0031-6903, 1347-5231
    • Year and Date
      2020-05-01
    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of Antibody-Oligonucleotide Complexes for targeting Exosomal microRNA.2020

    • Author(s)
      Asako Yamayoshi, Shota Oyama, Yusuke Kishimoto, Ryo Konishi, Tsuyoshi Yamamoto, Akio Kobori, Hiroshi Harada, Eishi Ashihara, Hiroshi Sugiyama, Akira Murakami.
    • Journal Title

      Pharmaceutic

      Volume: 12 Issue: 6 Pages: 545-545

    • DOI

      10.3390/pharmaceutics12060545

    • NAID

      120006988115

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hydrazide Derivatives of Luminol for Chemiluminescence-Labelling of Macromolecules2019

    • Author(s)
      Shibata Takayuki、Yoshimura Hiroki、Yamayoshi Asako、Tsuda Nobuaki、Dragusha Shpend
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 67 Issue: 8 Pages: 772-774

    • DOI

      10.1248/cpb.c19-00126

    • NAID

      130007686306

    • ISSN
      0009-2363, 1347-5223
    • Year and Date
      2019-08-01
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Selective cross-linking behavior of oligodeoxyribonucleotides containing 2'-O-[N-(4,5',8-trimethylpsoralen-4'- ylmethylcarbamoyl)]adenosine to mutant H-ras DNA2019

    • Author(s)
      A.Yamayoshi, M.Higuchi, Y.Sakai, A.Kobori, T.Yamamoto, T. Shibata, A. Murakami
    • Journal Title

      NUCLEOSIDES, NUCLEOTIDES AND NUCLEIC ACIDS

      Volume: 39 Issue: 1-3 Pages: 119-130

    • DOI

      10.1080/15257770.2019.1677912

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of modular conjugation strategy for N-acetylgalactosamine-targeted antisense oligonucleotides2019

    • Author(s)
      Yamamoto Tsuyoshi、Sawamura Motoki、Terada Chisato、Kashiwada Koki、Wada Fumito、Yamayoshi Asako、Obika Satoshi、Harada-Shiba Mariko
    • Journal Title

      Nucleosides, Nucleotides and Nucleic Acids

      Volume: 39 Issue: 1-3 Pages: 1-10

    • DOI

      10.1080/15257770.2019.1677911

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of Monovalent N ‐Acetylgalactosamine Phosphoramidite for Liver‐Targeting Oligonucleotides2019

    • Author(s)
      Yamamoto Tsuyoshi、Terada Chisato、Kashiwada Koki、Yamayoshi Asako、Harada‐Shiba Mariko、Obika Satoshi
    • Journal Title

      Current Protocols in Nucleic Acid Chemistry

      Volume: 78 Issue: 1 Pages: 1-18

    • DOI

      10.1002/cpnc.99

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Photochromic DNA having fluorescent protein-inspired nucleosides2018

    • Author(s)
      Akio Kobori, Taichiro Arai, Yuya Sakata, Takayuki Sugita, Asako Yamayoshi, Akira Murakami
    • Journal Title

      Tetrahedron Letters

      Volume: 59 Issue: 41 Pages: 3690-3693

    • DOI

      10.1016/j.tetlet.2018.08.064

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] エクソソーム表面抗原を利用した新しい創薬モダリティ2021

    • Author(s)
      山吉麻子
    • Organizer
      高分子学会九州支部女性研究者創発フォーラム
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 光架橋性プローブを用いたゲノムDNA中の メチル化シトシン検出技術の開発2021

    • Author(s)
      小嶋厚弘、山本剛史、嶋田直彦、丸山厚、山吉麻子
    • Organizer
      日本薬学会第141回年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 肺がん細胞に対するエクソソーム随伴型薬物送達システムの有効性評価2021

    • Author(s)
      大山将大、錦織大介、山本剛史、吉田藍子、大場雄介、山吉麻子
    • Organizer
      日本薬学会第141回年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] エピジェネティック修飾遺伝子を標的とした新規光応答性核酸の開発2021

    • Author(s)
      土井絹華、肥田千年星、山本剛史、堂野主税、和田健彦、山吉麻子
    • Organizer
      日本薬学会第141回年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] ソラレン導入型核酸の二重鎖DNAに対する光架橋特性の評価2021

    • Author(s)
      中尾樹希、江島穂乃香、山本剛史、堂野主税、和田健彦、山吉麻子
    • Organizer
      日本薬学会第141回年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 点突然変異遺伝子の発現制御を目指した光応答核酸の開発2021

    • Author(s)
      田原遼、酒井結、山本剛史、堂野主税、和田健彦、山吉麻子
    • Organizer
      日本薬学会第141回年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] (2S,4S)-ピロリジンPNAの合成と結合能評価2021

    • Author(s)
      安冨由加梨、寺田知邑、山吉麻子、山本剛史
    • Organizer
      日本薬学会第141回年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 肝臓指向型アンチセンス核酸の動態改善に向けた 新規GalNAcリガンドの構築と活性評価2021

    • Author(s)
      寺田知邑、和田郁人、 山吉麻子、斯波真理子、小比賀聡、山本剛史
    • Organizer
      日本薬学会第141回年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] エクソソームをハイジャックする抗体結合型核酸医薬2020

    • Author(s)
      山吉麻子
    • Organizer
      日本薬剤学会第35回年会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] エクソソーム随伴導入型薬物送達システムから「物質共生」を考える2020

    • Author(s)
      山吉麻子
    • Organizer
      静岡県立大学第288回 月例薬学セミナー
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 3-Amino-1,2-Propanediol-Linked Monomeric GalNAc Phosphoramidite For Efficient Delivery Of Antisense Oligonucleotides To Hepatocytes2020

    • Author(s)
      TERADA, Chisato; WADA, Fumito; YAMAYOSHI, Asako; HARADA-SHIBA, Mariko; OBIKA, Satoshi; YAMAMOTO, Tsuyoshi
    • Organizer
      16th Annual Meeting of the Oligonucleotide Therapeutics Society
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] エクソソーム随伴型薬物送達システムによる 核酸医薬の細胞内送達と免疫応答の検証2020

    • Author(s)
      大山将大, 富田真央, 錦織大介, 山本剛史, 山吉麻子
    • Organizer
      第36回日本DDS学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] エクソソーム随伴型薬物送達システムによる核酸医薬の細胞内送達2020

    • Author(s)
      山吉麻子、大山将大、錦織大介、和田健彦、山本剛史
    • Organizer
      第14回バイオ関連化学シンポジウム
    • Related Report
      2020 Annual Research Report
  • [Presentation] エクソソーム随伴型薬物送達システムによるsiRNAの細胞内送達と免疫応答の検証2020

    • Author(s)
      大山将大、富田真央、 山本剛史、山吉麻子
    • Organizer
      日本薬学会 第140年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 肝臓標的化核酸医薬のための新規N-アセチルガラクトサミンリガンドの開発2020

    • Author(s)
      寺田知邑、山吉麻子、 山本剛史
    • Organizer
      日本薬学会 第140年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Development of novel drug delivery system for targeting circulating microRNAs2019

    • Author(s)
      Asako Yamayoshi, Mao Tomita, Shota Oyama, Tsuyoshi Yamamoto
    • Organizer
      19th Symposium for Gene・Design and Delivery
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 遺伝子の非コード領域を標的とした機能性核酸開発2019

    • Author(s)
      山吉 麻子
    • Organizer
      第22回生命化学研究会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Photochemistry of psoralen-conjugated oligonucleotides targeting double-stranded DNA with epigenetic modifications2019

    • Author(s)
      Asako Yamayoshi, Chitose Hida, Juki Nakao, Tsuyoshi Yamamoto, Takehiko Wada, and Kazuhiko Nakatani
    • Organizer
      CISNAC2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] NOVEL DRUG DELIVERY SYSTEM FOR TARGETING EXOSOMAL MICRORNA2019

    • Author(s)
      Asako Yamayoshi, Shota Oyama, Mao Tomita, Emi Soma, Eishi Ashihara, Tsuyoshi Yamamoto
    • Organizer
      OTS2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development of novel drug delivery system for targeting circulating microRNAs2019

    • Author(s)
      Asako Yamayoshi
    • Organizer
      19th Symposium for Gene・Design and Delivery
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 光架橋性プローブを用いたゲノムDNA中のメチル化シトシン検出技術の開発2019

    • Author(s)
      小嶋厚弘、山本剛史、 嶋田直彦、丸山厚、 山吉麻子
    • Organizer
      第36回日本薬学会九州支部大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 遺伝子の非コード領域の機能制御を目指した人工核酸の開発2019

    • Author(s)
      山吉麻子
    • Organizer
      アライアンス・展開Bプロジェクトと科研費特別推進研究「リピート結合分子をプローブとしたトリヌクレオチドリピート病の化学生物学研究に関連する核酸科学ミニシンポジウム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 光をトリガーとした遺伝子発現制御法の開発2019

    • Author(s)
      山吉麻子
    • Organizer
      第3期 第4回 レーザー学会「レーザーバイオ医療」技術専門委員会(日本、長崎)
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] エクソソーム随伴導入型薬物送達システムの開発2019

    • Author(s)
      山吉麻子
    • Organizer
      日本薬学会第139回年会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Development of novel photoresponsive olugonucleotides targeting epigenetic DNA modifications2018

    • Author(s)
      Asako Yamayoshi
    • Organizer
      China-Japan Joint Symposium on Biomaterials 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 遺伝子の非コード領域が担う生命現象の支配を目指した機能性核酸の創製2018

    • Author(s)
      山吉麻子
    • Organizer
      第54回歯工学連携講演会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 遺伝子の非コード領域の機能制御を目指した人工核酸の創製2018

    • Author(s)
      山吉麻子
    • Organizer
      第11回佐賀分子標的治療研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 遺伝子の非コード領域が担う生命現象の支配を目指した機能性分子の創製2018

    • Author(s)
      山吉麻子
    • Organizer
      九州脳神経外科コンソーシアム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 体液中microRNAを標的とした遺伝子制御分子の開発とDDS2018

    • Author(s)
      山吉麻子
    • Organizer
      第34回日本DDS学会学術集会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 遺伝子発現のエピジェネティック制御機構を標的とした機能性核酸の創製 ~共同研究拠点制度で展開できた研究成果と人材育成~2018

    • Author(s)
      山吉麻子
    • Organizer
      第8回物質・デバイス領域共同研究拠点活動報告会及び平成29年度ダイナミック・アライアンス成果報告会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] NOVEL ANTIBODY-MEDIATED DRUG DELIVERY SYSTEM FOR TARGETING EXOSOMAL MICRORNA2018

    • Author(s)
      Asako Yamayoshi, Ryo Konishi, Akio Kobori, Naoto Yamashita, Eishi Ashihara, Akira Murakami, Hiroshi Sugiyama 
    • Organizer
      International Society for Extracellular Vesicles 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Development of novel drug delivery system for targeting exosomal microRNA2018

    • Author(s)
      Asako Yamayoshi,Tomohiro Narita, Hiroshi Sugiyama
    • Organizer
      18th Symposium for Gene・Design and Delivery
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Functional Regulation of Epigenetic DNA Modifications using Photoreactive Oligonucleotides2018

    • Author(s)
      Asako Yamayoshi, Takayuki Shibata, Yui Sakai, Takeshi Yamada, Tsuyoshi Yamamoto, Takehiko Wada, Kazuhiko Nakatani
    • Organizer
      The 45nd International Symposium on Nucleic Acids Chemistry
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 遺伝子の非コード領域の機能制御を目指した人工核酸の開発2018

    • Author(s)
      山吉麻子、柴田孝之, 和田健彦, 中谷和彦, 杉山弘
    • Organizer
      第28回 バイオ・高分子シンポジウム
    • Related Report
      2018 Annual Research Report
  • [Book] 核酸化学ハンドブック: microRNA (miRNA)2020

    • Author(s)
      山本剛史、山吉麻子*
    • Publisher
      講談社サイエンティフィック
    • Related Report
      2019 Annual Research Report
  • [Book] 医薬品開発における中分子領域(核酸医薬・ペプチド医薬品)での開発戦略:核酸医薬品の各作用機序と関連研究事例 miRNA標的2019

    • Author(s)
      山吉麻子
    • Total Pages
      206
    • Publisher
      株式会社情報機構
    • Related Report
      2019 Annual Research Report
  • [Remarks] エクソソーム含有miRNAを標的とした抗体結合型核酸を開発

    • URL

      https://www.nagasaki-u.ac.jp/ja/about/info/science/science206.html

    • Related Report
      2020 Annual Research Report
  • [Remarks] 長崎大学薬学部能性分子化学分野

    • URL

      http://www.ph.nagasaki-u.ac.jp/lab/function/index-j.html

    • Related Report
      2019 Annual Research Report
  • [Remarks] 長崎大学 薬学部 機能性分子化学分野

    • URL

      http://www.ph.nagasaki-u.ac.jp/lab/function/index-j.html

    • Related Report
      2018 Annual Research Report

URL: 

Published: 2018-04-23   Modified: 2023-01-30  

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