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Development of a novel RNA trans-splicing molecule for cancer gene therapy targeting to cancer-type organic anion transporting polypeptide 1B3

Research Project

Project/Area Number 15K14994
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Medical pharmacy
Research InstitutionChiba University

Principal Investigator

Furihata Tomomi  千葉大学, 大学院医学研究院, 助教 (80401008)

Co-Investigator(Kenkyū-buntansha) 下里 修  千葉県がんセンター(研究所), 発がん研究グループ DNA損傷シグナル研究室, 上席研究員 (30344063)
Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordscancer-type OATP1B3 / がん遺伝子治療 / がん / Cancer-type OATP1B3 / がん型OATP1B3 / がん個別化治療
Outline of Final Research Achievements

Spliceosome-mediated RNA trans-splicing, which is mediated by an RNA trans-splicing molecule (RTM), is expected to be a promising tool for cancer gene therapy. RTM leads to trans-splicing between a target mRNA and a suicide gene (such as the herpes simplex virus thymidine kinase) to generate the suicide protein. Therefore, we aimed at development and characterization of an RTM targeting to Ct-OATP1B3 mRNA (hereafter referred to as RTM44-2), which is expressed in various cancer tissues in a cancer-specific manner. To examine the RTM44-2 functionality, we developed LS180 cells stably expressing RTM44-2 (RTM/LS), and cytotoxic assays were performed using ganciclovir (GCV). As a result. GCV significantly reduced the viability of RTM/LS cells. Furthermore, such anti-cancer effects of the RTM-GCV system was also observed in vivo xenograft models. To summarize, our results indicate that the Ct-OATP1B3-targeted gene therapy has a potential to become an effective anti-cancer therapy.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (6 results)

All 2016 2015 Other

All Int'l Joint Research (2 results) Presentation (4 results) (of which Int'l Joint Research: 1 results)

  • [Int'l Joint Research] EB haus(オーストリア)

    • Related Report
      2016 Annual Research Report
  • [Int'l Joint Research] EB house(オーストリア)

    • Related Report
      2015 Research-status Report
  • [Presentation] 新規がん診断分子候補Ct-OATP1B3 mRNAはがん由来エキソソームに内包される2016

    • Author(s)
      井手秀行、 孫雨晨、 原田まなみ、 下里修、 上條岳彦、 山口直人、 千葉寬、 秋田英万、 安西尚彦、 降幡知巳
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(横浜市・神奈川県)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] Development and preclinical evaluation of a novel RNA trans-splicing molecule for cancer gene therapy targeted to cancer-type organic anion transporting polypeptide 1B32016

    • Author(s)
      Manami Harada, Tomomi Furihata, Yuchen Sun, Hidetaka Akita, Naohiko Anzai, Ulrich Koller, Anna Stierschneider, Josefina Pinon Hofbauer, Christina Gruber, Kan Chiba
    • Organizer
      第22回日本遺伝子細胞治療学会 年次学術集会
    • Place of Presentation
      虎ノ門ヒルズフォーラム(東京都)
    • Year and Date
      2016-07-28
    • Related Report
      2016 Annual Research Report
  • [Presentation] Cancer-type organic anion transporting polypeptide 1B3: current knowledge of expression profile, functional insights, and clinical perspectives2016

    • Author(s)
      Tomomi Furihata
    • Organizer
      Joint Symposium of Japanese Society for the Study on Xenobiotics (JSSX)- Korean Society of Applied Pharmacology (KSAP) at 31st Annual meeting of JSSX
    • Place of Presentation
      キッセイ文化ホール(松本市・長野県)
    • Related Report
      2016 Annual Research Report
  • [Presentation] Targeting cancer-type SLCO1B3 in the therapy of recessive dystrophic epidermolysis bullosa-associated squamous cell carcinoma2015

    • Author(s)
      Pinon Hofbauer J, Koller U, Stierschneider A, Hainzl S, Kocher T, Furihata T, South AP, Bauer JW, Gruber C.
    • Organizer
      Society for Investigative Dermatology Annual Meeting
    • Place of Presentation
      Atlanta, U.S.A.
    • Year and Date
      2015-05-06
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2018-03-22  

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