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2013 Fiscal Year Final Research Report

Development of novel cancer therapy using miRNA containing exosome

Research Project

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Project/Area Number 23390087
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Human pathology
Research InstitutionTokyo Medical University

Principal Investigator

KURODA Masahiko  東京医科大学, 医学部, 教授 (80251304)

Co-Investigator(Kenkyū-buntansha) OCHIYA Takahiro  独立行政法人国立がん研究センター, 研究所, 分野長 (60192530)
SUDO Katsuko  東京医科大学, 医学部, 兼任講師 (50126091)
Project Period (FY) 2011-04-01 – 2014-03-31
Keywordsエクソソーム / microRNA / EGFR / 分子標的治療
Research Abstract

Despite the therapeutic potential of nucleic acid drugs, their clinical application has been limited in part by a lack of appropriate delivery systems. Exosomes or microvesicles are small endosomally derived vesicles that are secreted by a variety of cell types and tissues. Here, we show that exosomes can efficiently deliver microRNA to epidermal growth factor receptor (EGFR)-expressing breast cancer cells. Targeting was achieved by engineering the donor cells to express the transmembrane domain of platelet-derived growth factor receptor fused to the GE11 peptide. Intravenously injected exosomes delivered let-7a microRNA to EGFR-expressing xenograft breast cancer tissue in Rag2-/- mice. Furthermore, we developed mimic miRNA that have efficient loading activity of the RISC complex. Our results suggest that exosomes can be used therapeutically to target EGFR-expressing cancerous tissues with nucleic acid drugs.

  • Research Products

    (50 results)

All 2014 2013 2012 2011 Other

All Journal Article (13 results) (of which Peer Reviewed: 12 results) Presentation (36 results) (of which Invited: 4 results) Remarks (1 results)

  • [Journal Article] KLF5 regulates the integrity and oncogenicity of intestinal stem cells2014

    • Author(s)
      Nakaya T, Ogawa S, Fukayama M, Kuroda M, Nagai R.(12名11番目)
    • Journal Title

      Cancer Res

      Volume: 74(10) Pages: 2882-91

    • DOI

      10.1158/0008-5472.CAN-13-2574

    • Peer Reviewed
  • [Journal Article] Activin receptor-like kinase5 inhibition suppresses mouse melanoma by ubiquitin degradation of Smad4, thereby derepressing eomesodermin in cytotoxic T lymphocytes2013

    • Author(s)
      Yoon JH, Sudo K, Kuroda M. (18 名 15 番目)
    • Journal Title

      EMBO molecular Medicine

      Volume: 5(11) Pages: 1720-39

    • DOI

      10.1002/emmm.201302524

    • Peer Reviewed
  • [Journal Article] Estrogen and estrogen receptor induce matrix metalloproteinase (MMP)-26 expression in endometrial carcinomacells2013

    • Author(s)
      Nishi H, Kuroda M, Isaka K
    • Journal Title

      Oncol Rep

      Volume: 30(2) Pages: 751-6

    • DOI

      10.3892/or.2013.2527

    • Peer Reviewed
  • [Journal Article] GRK6 deficiency in mice causes autoimmune disease due to impaired apoptotic cell clearance2013

    • Author(s)
      Nakaya M, Tajima M, Kuroda M.(18 名 16)
    • Journal Title

      Nature Communications

      Volume: 4 Pages: 1532

    • DOI

      10.1038/ncomms2540

    • Peer Reviewed
  • [Journal Article] The expression level of miR-18b in hepatocellular carcinoma is associated with the grade of malignancy and prognosis2013

    • Author(s)
      Murakami Y, Kuroda M.(14 名 14 番目)
    • Journal Title

      BMC Cancer

      Volume: 4 Pages: 13-99

    • DOI

      10.1186/1471-2407-13-99

    • Peer Reviewed
  • [Journal Article] Human adipose tissue-derived mesenchymal stem cells secrete functional neprilysin-bound exosomes2013

    • Author(s)
      Katsuda T, Tsuchiya R, Kosaka N, Kuroda M, Ochiya T. (10 名 9 番 目)
    • Journal Title

      SCIENTIFIC REPORTS

      Volume: 3 Pages: 1197

    • DOI

      10.1038/srep01197

    • Peer Reviewed
  • [Journal Article] Systemically Injected Exosomes Targeted to EGFR Deliver Antitumor MicroRNA to Breast Cancer Cells2013

    • Author(s)
      Ohno S, Takanashi M, Sudo K, Ohgi T, Ochiya T, Kuroda M.(12 名 9 番目)
    • Journal Title

      Molecular Therapy

      Volume: 21(1) Pages: 185-191

    • DOI

      10.1038/mt.2012.180

    • Peer Reviewed
  • [Journal Article] Leukemia cell to endothelial cell communication via exosomal miRNAs2013

    • Author(s)
      Umezu T, Ohyashiki K, Kuroda M, Ohyashiki JH
    • Journal Title

      Oncogene

      Volume: 32(22) Pages: 2747-55

    • DOI

      10.1038/onc.2012.295

    • Peer Reviewed
  • [Journal Article] Roles of exosomes and microvesicles in disease pathogenesis2013

    • Author(s)
      Ohno S, Ishikawa A, Kuroda M
    • Journal Title

      Advanced Drug Delivery Reviews

      Volume: 65(3) Pages: 398-401

    • DOI

      10.1016/j.addr.2012.07.019

    • Peer Reviewed
  • [Journal Article] LGR5-positive colon cancer stem cells interconvert with drug-resistant LGR5-negative cells and are capable of tumor reconstitution2012

    • Author(s)
      Kobayashi S, Yamada-Okabe H, Suzuki M, Natori O, Kato A, Ochiya T, Kuroda M. (22名 20 番目)
    • Journal Title

      Stem Cells

      Volume: 30(12) Pages: 2631-44

    • DOI

      10.1002/stem.1257

    • Peer Reviewed
  • [Journal Article] Efficacy of a Novel Class of RNA Interference Therapeutic Agents2012

    • Author(s)
      Hamasaki T, Suzuk H, Morser J, Kuroda M, Ochiya T, Gabazza EC, Ohgi T.(19 名15 番目)
    • Journal Title

      PLoS One

      Volume: 7(8) Pages: e42655

    • DOI

      10.1371/journal.pone.0042655

    • Peer Reviewed
  • [Journal Article] Isolation of miRNAs that target EGFR mRNA in human lung cancer2012

    • Author(s)
      Yamaguchi G, Takanashi M, Tanaka M, Fujita K, Ohira T, Kuroda M, Ikeda N
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 420(2) Pages: 411-6

    • DOI

      10.1016/j.bbrc.2012.03.008

    • Peer Reviewed
  • [Journal Article] miR-92 is a key oncogenic component of the miR-17-92 cluster in colon cancer2011

    • Author(s)
      Tsuchida A, Ohno S, Wu W, Borjigin N, Fujita K, Aoki T, Ueda S, Takanashi M, Kuroda M
    • Journal Title

      Cancer science

      Volume: 102(12) Pages: 2264-71

    • DOI

      10.1111/j.1349-7006.2011.02081.x

  • [Presentation] Novel RNAi agent can control HCV replication2014

    • Author(s)
      Kuroda M
    • Organizer
      AACR Annual Meeting 2014
    • Place of Presentation
      San Diego, CA
    • Year and Date
      20140405-09
  • [Presentation] Significance and applications of novel class of RNA for cancer therapy2014

    • Author(s)
      黒田 雅彦
    • Organizer
      Drug Discovery World Asia
    • Place of Presentation
      @Suntec Singapore Convention & Exhibition Centre
    • Year and Date
      20140311-12
    • Invited
  • [Presentation] Novel RNAi agent can control HCV replication2014

    • Author(s)
      Kuroda M
    • Organizer
      RNA Silencing(A9) Keystone symposia
    • Place of Presentation
      Seattle Washington, USA
    • Year and Date
      20140131-0205
  • [Presentation] 肺がんを効果的に抑制する Mimic microRNA の新規形状の探索2014

    • Author(s)
      黒田 雅彦
    • Organizer
      第103回日本病理学会総会
    • Place of Presentation
      広島
    • Year and Date
      2014-04-26
  • [Presentation] 自己由細胞由来のエクソソームによるドラッグデリバリーシステムへの応用2014

    • Author(s)
      黒田 雅彦
    • Organizer
      第103回日本病理学会総会
    • Place of Presentation
      広島
    • Year and Date
      2014-04-26
  • [Presentation] 核酸医薬品の開発2014

    • Author(s)
      黒田 雅彦
    • Organizer
      日本がん分子標的治療学会
    • Place of Presentation
      東京
    • Year and Date
      2014-01-17
    • Invited
  • [Presentation] Development of nucleic acid therapy2013

    • Author(s)
      Kuroda M
    • Organizer
      RNAi, MicroRNAs & Single Cell Biology-2013 Meeting
    • Place of Presentation
      Waltham USA
    • Year and Date
      20130501-02
    • Invited
  • [Presentation] KLF5 is essential for oncogenesis of intestinal tumors and control of intestinal stem cells2013

    • Author(s)
      Kuroda M
    • Organizer
      AACR Annual Meeting 2013
    • Place of Presentation
      Washington, DC
    • Year and Date
      20130406-10
  • [Presentation] Systemically injected exosomes targeted to EGFR deliver anti-tumor microRNA to breast cancer cells2013

    • Author(s)
      Kuroda M
    • Organizer
      Keystone Symposia Conference - Noncoding RNAs in Development and Cancer(A7)
    • Place of Presentation
      Vancouver, British Columbia, CA
    • Year and Date
      20130120-25
  • [Presentation] miRNA 医薬品の開発2013

    • Author(s)
      黒田 雅彦
    • Organizer
      第6回岐阜大学先端創薬医療シンポジウム
    • Place of Presentation
      東京 ( コクヨホール )
    • Year and Date
      2013-11-29
  • [Presentation] 疾患関連 miRNA を標的にした臨床医薬品の開発2013

    • Author(s)
      黒田 雅彦
    • Organizer
      第40回日本臓器保存生物医学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2013-11-10
  • [Presentation] シンポジウム 6. 新規の lipid conjugate RNA を用いたがん治療法の開発2013

    • Author(s)
      黒田 雅彦
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2013-10-05
  • [Presentation] 核酸医薬品の開発のためのトランスレーショナルリサーチ2013

    • Author(s)
      黒田 雅彦
    • Organizer
      日経バイオテクオンラインプロフェッショナルセミナー
    • Place of Presentation
      東京
    • Year and Date
      2013-09-24
  • [Presentation] Exosome によるがん特異的miRNA デリバリー法の開発2013

    • Author(s)
      黒田 雅彦
    • Organizer
      第29回日本D DS学会学術集会, シンポジウム
    • Place of Presentation
      京都
    • Year and Date
      2013-07-05
    • Invited
  • [Presentation] ワークショップ 12 バイオマーカーの病理研究・治療への応用 microRNA の病理研究・治療への応用2013

    • Author(s)
      黒田 雅彦
    • Organizer
      第102回日本病理学会総会
    • Place of Presentation
      札幌
    • Year and Date
      2013-06-07
  • [Presentation] KLF5 functions as the master regulator of the integrity and oncogenicity of intestinal stem cells2013

    • Author(s)
      黒田雅彦
    • Organizer
      第102回日本病理学会総会
    • Place of Presentation
      札幌
    • Year and Date
      2013-06-07
  • [Presentation] 前立腺癌におけるmicroRNA-200cの発現解析2013

    • Author(s)
      黒田 雅彦
    • Organizer
      第102回日本病理学会総会
    • Place of Presentation
      札幌
    • Year and Date
      2013-06-07
  • [Presentation] 細気管支肺胞上皮癌におけるRAS と let-7 の発現の特徴2013

    • Author(s)
      黒田 雅彦
    • Organizer
      第102回日本病理学会総会
    • Place of Presentation
      札幌
    • Year and Date
      2013-06-07
  • [Presentation] マウスに経口投与したエクソソームの生体内での安定性と分布2012

    • Author(s)
      黒田 雅彦
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Year and Date
      20120919-21
  • [Presentation] The infection of hepatitis C virus activates the exosomes and microvesicles secretion pathway of host cells2012

    • Author(s)
      黒田 雅彦
    • Organizer
      第4回日本RNAi 研究会
    • Place of Presentation
      広島
    • Year and Date
      20120830-0901
  • [Presentation] Novel type of small RNA exhibit RNA interference effect without activation of Toll-like receptor 32012

    • Author(s)
      Kuroda M
    • Organizer
      キーストンシンポジア(Nucleic Acid Therapeutics : From Base Pairs to Bedsides (A2)
    • Place of Presentation
      santa Fe, New Mexico USA
    • Year and Date
      20120110-15
  • [Presentation] 大腸癌発生における形態異常とmiRNA2012

    • Author(s)
      黒田 雅彦
    • Organizer
      第71回日本癌学会学術総会
    • Place of Presentation
      札幌
    • Year and Date
      2012-09-21
  • [Presentation] 核酸創薬の現状と課題, 今後の方向2012

    • Author(s)
      黒田 雅彦
    • Organizer
      日経バイオテクプロフェッショナルセミナー
    • Place of Presentation
      東京
    • Year and Date
      2012-05-28
  • [Presentation] EGFR リガンド発現エクソソームを用いた新規ドラッグデリバリーシステムの開発2012

    • Author(s)
      黒田 雅彦
    • Organizer
      第101回日本病理学会総会
    • Place of Presentation
      東京
    • Year and Date
      2012-04-27
  • [Presentation] 胃低分化癌における in situ hybridization 法を用いた miRNA-92a および200c の発現低下の意義2012

    • Author(s)
      黒田 雅彦
    • Organizer
      第101回日本病理学会総会
    • Place of Presentation
      東京
    • Year and Date
      2012-04-26
  • [Presentation] Delivery of miRNA to the EGFR-expressed tumor by systemic injection of target exosomes2012

    • Author(s)
      Kuroda M
    • Organizer
      International Society for the EGFR-extracellular Vesicled (ISEV)
    • Place of Presentation
      Gothenburg, Sweden
    • Year and Date
      2012-04-18
  • [Presentation] Selective target delivery of miRNA using EGF expressing exosomes2012

    • Author(s)
      Kuroda M
    • Organizer
      Keystone Symposia on Molecular and Cellular Biology
    • Place of Presentation
      Santa Fe, New Mexico USA
    • Year and Date
      2012-01-12
  • [Presentation] リガンド修飾エクソソームによるEGF receptor 発現細胞を標的としたドラッグデリバリーシステムの開発2011

    • Author(s)
      黒田 雅彦
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      20111003-04
  • [Presentation] Delivery of antitumor molecules to the EGFR expressing cancer using EGF expressing exosomes2011

    • Author(s)
      Kuroda M
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      横浜
    • Year and Date
      2011-12-16
  • [Presentation] 人工型エクソソームを用いた新規肺癌治療の開発2011

    • Author(s)
      黒田 雅彦
    • Organizer
      第52回日本肺癌学会総会
    • Place of Presentation
      大阪
    • Year and Date
      2011-11-04
  • [Presentation] 乳がん幹細胞の維持に関与するmicroRNA の探索2011

    • Author(s)
      黒田 雅彦
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-10-05
  • [Presentation] 血管内皮細胞による癌細胞由来exosomal miRNA の取り込み機構の解明2011

    • Author(s)
      黒田 雅彦
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-10-05
  • [Presentation] CD63-GFP を発現したエクソソームのマウス生体内での安定性と分布について2011

    • Author(s)
      黒田 雅彦
    • Organizer
      第70回日本癌学会学術総会
    • Place of Presentation
      名古屋
    • Year and Date
      2011-10-05
  • [Presentation] 疾患マーカーとしての細胞外核酸( 分泌型 miRNA)2011

    • Author(s)
      黒田 雅彦
    • Organizer
      第84回日本生化学会大会 ( シンポジウム )
    • Place of Presentation
      京都
    • Year and Date
      2011-09-24
  • [Presentation] 乳がん幹細胞に対する核酸医薬の開発2011

    • Author(s)
      黒田 雅彦
    • Organizer
      第2回久留米核酸医薬研究会
    • Place of Presentation
      福岡
    • Year and Date
      2011-05-11
  • [Presentation] 人口型 exosome の生体内分布と安定性についての研究2011

    • Author(s)
      黒田 雅彦
    • Organizer
      第100回日本病理学会総会
    • Place of Presentation
      横浜
    • Year and Date
      2011-04-30
  • [Remarks]

    • URL

      http://www.tokyo-med.ac.jp/molpathol/

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Published: 2015-06-25  

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