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Development of an adenovirus vector containing microRNA-regulated gene expression system

Research Project

Project/Area Number 20689004
Research Category

Grant-in-Aid for Young Scientists (A)

Allocation TypeSingle-year Grants
Research Field Medical pharmacy
Research InstitutionNational Institute of Biomedical Innovation

Principal Investigator

SAKURAI Fuminori  National Institute of Biomedical Innovation, 大学院・薬学研究科, 准教授 (70370939)

Research Collaborator MIZUGUCHI Hiroyuki  大阪大学, 大学院・薬学研究科, 教授
KAWABATA Kenji  (独)医薬基盤研究所, 幹細胞制御プロジェクト, プロジェクトリーダー
KATAYAMA Kazufumi  大阪大学, 大学院・薬学研究科, 助教
TASHIRO Katsuhisa  (独)医薬基盤研究所, 幹細胞制御プロジェクト, プロジェクト研究員
KONDOH Masuo  大阪大学, 大学院・薬学研究科, 准教授
YAGI Kiyohito  大阪大学, 大学院・薬学研究科, 教授
NAKAMURA Shin-ichiro  滋賀医科大学, 動物生命科学センター, 准教授
KAWASE Atsushi  近畿大学, 薬学部, 講師
IWAKI Masahiro  近畿大学, 薬学部, 教授
HAYAKAWA Takao  近畿大学, 薬学総合研究所, 所長
FUJIWARA Toshiyoshi  岡山大学, 医歯薬学総合研究科, 教授
SUZUKI Takayuki  大阪大学, 大学院・薬学研究科, 大学院生
SUGIO Kumiko  大阪大学, 大学院・薬学研究科, 大学院生
SHIMIZU Kahori  大阪大学, 大学院・薬学研究科, 大学院生
BENNETT David Mark Gilfedder  大阪大学, 大学院・薬学研究科, 大学院生
TOMITA Kyoko  大阪大学, 大学院・薬学研究科, 大学院生
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥25,350,000 (Direct Cost: ¥19,500,000、Indirect Cost: ¥5,850,000)
Fiscal Year 2010: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
Fiscal Year 2009: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
Fiscal Year 2008: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
Keywords遺伝子治療 / マイクロRNA / 発現制御 / 遺伝子導入ベクター / アデノウイルスベクター / 遺伝子発現制御 / 制限増殖型ウイルス / 癌治療 / 非特異的発現 / 制限増殖型アデノウイルス / 免疫応答 / 自殺遺伝子
Research Abstract

In this study, we developed the adenovirus (Ad) vectors which exhibited enhanced safety profiles by incorporating microRNA (miRNA)-regulated gene expression system. For example, (1)an Ad vector which shows reduction in the transgene expression in the liver and spleen by insertion of sequences complementary to liver- and spleen-specific miRNA, respectively, (2) an Ad vector which exhibits reduction in the leaky expression of Ad genes by insertion of miRNA complementary sequences into 3'-untranslated region of E2A or E4 genes, (3) a oncolytic Ad which shows reduced replication in normal cells by insertion of sequences complementary to normal cell-specific miRNAs, were developed.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (32 results)

All 2011 2010 2009 2008 Other

All Journal Article (14 results) (of which Peer Reviewed: 5 results) Presentation (15 results) Remarks (3 results)

  • [Journal Article] Enhanced Safety Profiles of the Telomerase-Specific Replication- Competent Adenovirus by Incorporation of Normal Cell-Specific microRNA-Targeted Sequences.2011

    • Author(s)
      Sugio K, Sakurai F, Katayama K, Tashiro K, Matsui H, Kawabata K, Kawase A, Iwaki M, Hayakawa T, Fujiwara T, Mizuguchi H
    • Journal Title

      Clin Cancer Res. 17

      Pages: 2807-2818

    • Related Report
      2010 Final Research Report
  • [Journal Article] Development of cellular and gene therapy products for bioacitve protein-based therapy.2010

    • Author(s)
      Sakurai F, Nishikawa M.
    • Journal Title

      Yakugaku Zasshi. 130

      Pages: 1487-1488

    • NAID

      130000451699

    • Related Report
      2010 Final Research Report
  • [Journal Article] Development of recombinant adenovirus carrying microRNA-regulated gene expression system.2010

    • Author(s)
      Sakurai F, Mizuguchi H
    • Journal Title

      Yakugaku Zasshi. 130

      Pages: 1497-1504

    • NAID

      130000451701

    • Related Report
      2010 Final Research Report
  • [Journal Article] Development of recombinant adenovirus carrying microRNA-regulated gene expression system2010

    • Author(s)
      Sakurai F, et al.
    • Journal Title

      Yakugaku Zasshi

      Volume: 130 Pages: 1497-1504

    • NAID

      130000451701

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of cellular and gene therapy products for bioacitve protein-based therapy2010

    • Author(s)
      Sakurai F, et al.
    • Journal Title

      Yakugaku Zasshi

      Volume: 130 Pages: 1487-8

    • NAID

      130000451699

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 遺伝子組換えウイルスの安全性向上に向けた遺伝子改変-microRNAによる遺伝子発現制御システムを搭載した組換えウイルスの開発-2009

    • Author(s)
      櫻井文教、川端健二、水口裕之
    • Journal Title

      Drug Delivery System. 24

      Pages: 572-581

    • Related Report
      2010 Final Research Report
  • [Journal Article] 遺伝子組換えウイルスの安全性向上に向けた遺伝子改変-microRNAによる遺伝子発現制御システムを搭載した組換えウイルスの開発-2009

    • Author(s)
      櫻井文教、川端健二、水口裕之
    • Journal Title

      Drug Delivery System 24

      Pages: 572-581

    • Related Report
      2009 Annual Research Report
  • [Journal Article] miR-122a-regulated expression of a suicide gene prevents hepatotoxicity without altering antitumor effects in suicide gene therapy.2008

    • Author(s)
      Suzuki T, Sakurai F, Nakamura S, Kouyama E, Kawabata K, Kondoh M, Yagi K, Mizuguchi H
    • Journal Title

      Mol Ther. 16

      Pages: 1719-1726

    • Related Report
      2010 Final Research Report
  • [Journal Article] miR-122a-regulated expression of a suicide gene prevents hepatotoxicity without disturbing the antitumor effects in suicide gene therapy2008

    • Author(s)
      Suzuki T, et al.
    • Journal Title

      Molecular Therapy 16

      Pages: 1719-1726

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MicroRNA-regulated Transgene Expression Systems for Gene Therapy and Virotherapy.

    • Author(s)
      Sakurai F, Katayama K, Mizuguchi H
    • Journal Title

      Frontier in Bioscience. (in press.)

    • Related Report
      2010 Final Research Report
  • [Journal Article] ウイルスベクターと遺伝子治療

    • Author(s)
      水口裕之、櫻井文教
    • Journal Title

      化学療法の領域 (印刷中)

    • Related Report
      2010 Final Research Report
  • [Journal Article] Enhanced safety profiles of the telomerase-specific replication-competent adenovirus by incorporation of normal cell-specific microRNA-targeted sequences

    • Author(s)
      Sugio K, Sakurai F, et al.
    • Journal Title

      Clinical Cancer Research

      Volume: (印刷中)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] MicroRNA-regulated Transgene Expression Systems for Gene Therapy and Virotherapy

    • Author(s)
      Sakurai F, et al.
    • Journal Title

      Frontier in Bioscience

      Volume: (印刷中)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ウイルスベクターと遺伝子治療

    • Author(s)
      水口裕之、櫻井文教
    • Journal Title

      化学療法の領域

      Volume: (印刷中)

    • Related Report
      2010 Annual Research Report
  • [Presentation] 非増殖型アデノウイルスベクターより非特異的に発現するウイルス遺伝子の定量的発現解析2011

    • Author(s)
      清水かほり, 櫻井文教, 他
    • Organizer
      日本薬学会第131年会
    • Place of Presentation
      静岡・ツインメッセ
    • Year and Date
      2011-03-29
    • Related Report
      2010 Annual Research Report
  • [Presentation] Recombinant adenoviruses carrying microRNA-regulated gene expression system.2010

    • Author(s)
      Sakurai F
    • Organizer
      The 9th China-Japan-Korea Foresight Joint Symposium on Gene Delivery and the International Workshop on Biomaterials 2010.
    • Place of Presentation
      China
    • Year and Date
      2010-06-21
    • Related Report
      2010 Final Research Report
  • [Presentation] Recombinant adenoviruses carrying microRNA-regulated gene expression system2010

    • Author(s)
      Sakurai F
    • Organizer
      The 9th China-Japan-Korea Foresight Joint Symposium on Gene Delivery and the International Workshop on Biomaterials 2010
    • Place of Presentation
      Graduate Complex, CIAC (China)(招待講演)
    • Year and Date
      2010-06-21
    • Related Report
      2010 Annual Research Report
  • [Presentation] マイクロRNAによる遺伝子発現制御システムを搭載した組換えアデノウイルスの開発2010

    • Author(s)
      櫻井文教、水口裕之
    • Organizer
      日本薬学会第130年会
    • Place of Presentation
      岡山
    • Year and Date
      2010-03-30
    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Presentation] microRNAを利用した制限増殖型アデノウイルスの安全性向上に関する検討2010

    • Author(s)
      櫻井文教, 他
    • Organizer
      第26回日本DDS学会
    • Place of Presentation
      大阪国際交流センター
    • Related Report
      2010 Annual Research Report
  • [Presentation] Targeting adenovirus vector transgene expression by exploiting endogenous microRNA expression and the Cre-loxP system2010

    • Author(s)
      David Bennett, 櫻井文教, 他
    • Organizer
      第26回日本DDS学会
    • Place of Presentation
      大阪国際交流センター
    • Related Report
      2010 Annual Research Report
  • [Presentation] Spleen-specific transgene expression by adenovirus vectors exploiting endogenous microRA expression and the Cre-loxP system2010

    • Author(s)
      David Bennett, 櫻井文教, 他
    • Organizer
      遺伝子・デリバリー研究会第10回シンポジウム
    • Place of Presentation
      北海道大学学術交流会館
    • Related Report
      2010 Annual Research Report
  • [Presentation] microRNAによる遺伝子発現制御システムを搭載した制限増殖型アデノウイルスの開発2010

    • Author(s)
      杉尾久美子、櫻井文教, 他
    • Organizer
      日本薬学会第130年会
    • Place of Presentation
      岡山
    • Related Report
      2009 Annual Research Report
  • [Presentation] マイクロRNAによる遺伝子発現制御システムを搭載した制限増殖型アデノウイルスの開発2009

    • Author(s)
      杉尾久美子、櫻井文教, 他
    • Organizer
      第25回日本DDS学会
    • Place of Presentation
      東京
    • Related Report
      2009 Annual Research Report
  • [Presentation] MiRNA-regulated expression of herpes simplex virus thymidine kinase prevents hepatotoxicity without disturbing antitumor effect in adenovirus vector-mediated suicide gene therapy.2008

    • Author(s)
      Sakurai F, Suzuki T, Nakamura S, Kouyama E, Kondoh M, Yagi K, Kawabata K, Mizuguchi H.
    • Organizer
      第14回日本遺伝子治療学会学術集会
    • Place of Presentation
      札幌
    • Related Report
      2010 Final Research Report
  • [Presentation] MicroRNA-regulated transgene expression system reduces unwanted side effects in adenovirus vector-mediated suicide gene therapy.2008

    • Author(s)
      Sakurai F, Suzuki T, Kondoh M, Yagi K, Kawabata K, Mizuguchi H.
    • Organizer
      11^<th> Annual Meeting of the American Society of Gene Therapy.
    • Place of Presentation
      Boston, USA
    • Related Report
      2010 Final Research Report
  • [Presentation] MicroRNA-regulated transgene expression system reduces unwantedside effects in adenovirus vector-mediated suicide gene therapy2008

    • Author(s)
      Fuminori Sakurai, et al
    • Organizer
      11th annual meeting of the American Society of gene therapy
    • Place of Presentation
      米国・ボストン
    • Related Report
      2008 Annual Research Report
  • [Presentation] MIRNA-REGULATED EXPRESSION OF HERPES SIMPLEX VIRUS THYMIDINE KINASE PREVENTS HEPATOTOXICITY WITHOUT DISTURBING ANTITUMOR EFFECT IN ADENOVIRUS VECTOR-MEDIATED SUICIDE GENE THERAPY2008

    • Author(s)
      Fuminori Sakurai, et al.
    • Organizer
      第14回JSGT学術集会
    • Place of Presentation
      札幌
    • Related Report
      2008 Annual Research Report
  • [Presentation] マイクロRNAを利用した腫瘍特異的な遺伝子発現能を搭載したアデノウイルスベクターの開発2008

    • Author(s)
      櫻井文教, 他
    • Organizer
      第24回日本DDS学会
    • Place of Presentation
      東京
    • Related Report
      2008 Annual Research Report
  • [Presentation] MicroRNAを利用した遺伝子発現制御機構を搭載したアデノウイルスベクターの開発2008

    • Author(s)
      櫻井文教, 他
    • Organizer
      第18回アンチセンスシンポジウム
    • Place of Presentation
      岐阜
    • Related Report
      2008 Annual Research Report
  • [Remarks] ホームページ等

    • URL

      https://sites.google.com/site/bunshiseibutugaku/

    • Related Report
      2010 Final Research Report
  • [Remarks]

    • URL

      https://sites.google.com/site/bunshiseibutugaku/

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.nibio.go.jp/Proj3HP/pub2011.html

    • Related Report
      2010 Annual Research Report

URL: 

Published: 2008-04-01   Modified: 2016-04-21  

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