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Development of adenovirus vector lacking VA RNA genes for efficient microRNA expression

Research Project

Project/Area Number 24701021
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Clinical oncology
Research InstitutionThe University of Tokyo

Principal Investigator

KONDO Saki  東京大学, 医科学研究所, 助教 (80451871)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
KeywordsmicroRNA / ウイルスベクター / 遺伝子治療 / アデノウイルスベクター / small RNA / 発現システム / shRNA
Research Abstract

Non-coding small RNAs are involved in tumorigenesis. Although the transfection system is used to examine the role of small RNAs, it is not applicable for in vivo studies. Adenovirus vector (AdV) is used to deliver small RNAs including short-hairpin RNA (shRNA) and microRNA (miRNA). However, this vector expresses virus-associated RNAs (VA RNAs). Since VA RNAs are processed using the same pathway as shRNAs, a question arises as to whether VA RNAs influence the RNAi strategy when this vector is used. It has not been tested because VA-deleted AdVs have been difficult to develop.
We established a method for VA-deleted AdV production. We compared the activities of shRNAs against hepatitis C Virus (HCV) expressed from VA-deleted AdVs with conventional AdVs. The VA-deleted AdVs inhibited HCV production much more efficiently. Therefore, VA-deleted AdVs were more effective than the current AdVs for shRNA downregulation, probably because of no competition between VA RNAs and the shRNAs.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (35 results)

All 2014 2013 2012

All Journal Article (3 results) (of which Peer Reviewed: 3 results) Presentation (28 results) Book (4 results)

  • [Journal Article] Efficient production of adenovirus vector lacking genes of virus-associated RNAs that disturb cellular RNAi machinery.2013

    • Author(s)
      Maekawa A, Pei Z, Suzuki M, Fukuda H, Ono Y, Kondo S, Saito I, Kanegae Y.
    • Journal Title

      Scientific Report

      Volume: 3 Issue: 1 Pages: 1136-1136

    • DOI

      10.1038/srep01136

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Adenovirus vectors lacking virus-associated RNA expression enhance shRNA activity to suppress hepatitis C virus replication.2013

    • Author(s)
      110. Pei Z, Shi G, Kondo S, Ito M, Maekawa A, Suzuki M, Saito I, Suzuki T, Kanegae Y.
    • Journal Title

      Scientific Reports

      Volume: 3 Issue: 1 Pages: 3575-3575

    • DOI

      10.1038/srep03575

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Efficient production of adenovirus vector lacking genes of virus-associated RNAs that disturb cellular RNAi machinery.2013

    • Author(s)
      Maekawa A., Pei Z., Suzuki M., Fukuda H., Ono Y., Kondo S., Saito I., and Kanegae Y.
    • Journal Title

      Scientific Report

      Volume: 39

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation]2013

    • Author(s)
      近藤小貴、前川文、裴崢、鈴木まりこ、斎藤泉、鐘ヶ江裕美
    • Organizer
      第19回日本遺伝子治療学会
    • Related Report
      2013 Final Research Report
  • [Presentation]2013

    • Author(s)
      近藤小貴、斎藤泉、鐘ヶ江裕美
    • Organizer
      第72回日本癌学会
    • Related Report
      2013 Final Research Report
  • [Presentation]2013

    • Author(s)
      Saki Kondo, Aya Maekawa, Mariko Suzuki, Yumi Kanegae and Izumu Saito
    • Organizer
      The 21th European Society of Gene and Cell Therapy collaborative Congress
    • Related Report
      2013 Final Research Report
  • [Presentation]2013

    • Author(s)
      近藤小貴、前川文、裴崢、鈴木まりこ、鐘ヶ江裕美、斎藤泉
    • Organizer
      第61回日本ウイルス学会
    • Related Report
      2013 Final Research Report
  • [Presentation]2013

    • Author(s)
      近藤小貴、前川文、裴崢、鈴木まりこ、鐘ヶ江裕美、斎藤泉
    • Organizer
      第36回日本分子生物学会
    • Related Report
      2013 Final Research Report
  • [Presentation] 宿主RNAi経路に影響を与えるvirus-associated RNAを欠失したアデノウイルスベクターの高効率作製法2013

    • Author(s)
      近藤小貴、前川文、裴崢、鈴木まりこ、斎藤泉、鐘ヶ江裕美
    • Organizer
      第19回日本遺伝子治療学会学術集会
    • Place of Presentation
      岡山コンベンションセンター(岡山)
    • Related Report
      2013 Annual Research Report
  • [Presentation] アデノウイルスベクターから発現しているウイルス由来miRNAsは細胞増殖関連遺伝子を制御する2013

    • Author(s)
      近藤小貴、斎藤泉、鐘ヶ江裕美
    • Organizer
      第72回日本癌学会学術総会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Therapeutic strategy of HBV using VA-deleted adenovirus vectors dually expressing shRNA and interferon2013

    • Author(s)
      Zheng Pei, Aya Maekawa, Mariko Suzuki, Yumi Kanegae, Saki Kondo, Izumu Saito
    • Organizer
      2013 International Meeting on Molecular Biology of Hepatitis B Viruses
    • Place of Presentation
      Shanghai Medical College Fudan University, Shanghai, China
    • Related Report
      2013 Annual Research Report
  • [Presentation] First-generation adenovirus vector expresses viral-associated (VA) RNAs that disturb cellular gene expressions2013

    • Author(s)
      Saki Kondo, Aya Maekawa, Mariko Suzuki, Yumi Kanegae, Izumu Saito
    • Organizer
      The 21th European Society of Gene and Cell Therapy collaborative Congress 2013
    • Place of Presentation
      Palacio Municipal de Congresos de Madrid, Madrid, Spain
    • Related Report
      2013 Annual Research Report
  • [Presentation] Dual-safe adenovirus vector lacking virus-associated RNA genes enhanced shRNA activity2013

    • Author(s)
      Yumi Kanegae, Aya Maekawa, Zheng Pei, Mariko Suzuki, Saki Kondo, Izumu Saito
    • Organizer
      The 21th European Society of Gene and Cell Therapy collaborative Congress 2013
    • Place of Presentation
      Palacio Municipal de Congresos de Madrid, Madrid, Spain
    • Related Report
      2013 Annual Research Report
  • [Presentation] Very efficient production of adenovirus vector lacking genes of virus-associated RNAs that disturb cellular RNAi machinery: safer alternative to current vector2013

    • Author(s)
      Aya Maekawa, Zheng Pei, Mariko Suzuki, Saki Kondo, Izumu Saito, Yumi Kanegae
    • Organizer
      The 21th European Society of Gene and Cell Therapy collaborative Congress 2013
    • Place of Presentation
      Palacio Municipal de Congresos de Madrid, Madrid, Spain
    • Related Report
      2013 Annual Research Report
  • [Presentation] アデノウイルスベクターから常に発現しているvirus-associated (VA) RNAは標的細胞内の遺伝子発現に影響を与える2013

    • Author(s)
      近藤小貴、前川文、裴崢、鈴木まりこ、鐘ヶ江裕美、斎藤泉
    • Organizer
      第61回日本ウイルス学会学術集会
    • Place of Presentation
      国際会議場(神戸)
    • Related Report
      2013 Annual Research Report
  • [Presentation] アデノウイルスベクターの目的遺伝子挿入領域と向きはベクター作製や発現効率に影響を与えるか:Dual発現vector作製に向けた検討2013

    • Author(s)
      鈴木まりこ、前川文、近藤小貴、鐘ヶ江裕美、斎藤泉
    • Organizer
      第61回日本ウイルス学会学術集会
    • Place of Presentation
      国際会議場(神戸)
    • Related Report
      2013 Annual Research Report
  • [Presentation] アデノウイルスベクターの問題点:ベクターがコードするVirus-associated (VA) RNAは宿主遺伝子発現に影響を与える2013

    • Author(s)
      近藤小貴、前川文、裴崢、鈴木まりこ、鐘ヶ江裕美、斎藤泉
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド(神戸)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 1つの細胞に多数のDNAコピーを導入出来るマルチコピーを保持したコスミドのトランスフェクションにおける有用性2013

    • Author(s)
      裴崢、近藤小貴、前川文、鈴木まりこ、鐘ヶ江裕美、斎藤泉
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド(神戸)
    • Related Report
      2013 Annual Research Report
  • [Presentation] E3領域への目的遺伝子の挿入はアデノウイルスベクター作製効率に影響を与えるか:ベクター/目的遺伝子キメラmRNAの生成2013

    • Author(s)
      鈴木まりこ、近藤小貴、鐘ヶ江裕美、斎藤泉
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド(神戸)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 細胞特異的長期発現持続型mini-adenovirus vector (mini-AdV)の開発2013

    • Author(s)
      前川文、裴崢、鈴木まりこ、吉岡貴史、近藤小貴、鐘ヶ江裕美、斎藤泉
    • Organizer
      第36回日本分子生物学会年会
    • Place of Presentation
      神戸ポートアイランド(神戸)
    • Related Report
      2013 Annual Research Report
  • [Presentation]2012

    • Author(s)
      近藤小貴、斎藤泉、Nic Jones
    • Organizer
      第18回日本遺伝子治療学会
    • Related Report
      2013 Final Research Report
  • [Presentation]2012

    • Author(s)
      近藤小貴、鐘ヶ江裕美、斎藤泉
    • Organizer
      第17回日本癌学会
    • Related Report
      2013 Final Research Report
  • [Presentation]2012

    • Author(s)
      Saki Kondo, Yumi Kanegae, Nic Jones, Izumu Saito
    • Organizer
      The 20th European Society of Gene and Cell Therapy meeting
    • Related Report
      2013 Final Research Report
  • [Presentation] A role of microRNAs for sensitization to cisplatin in ovarian cancer cell lines2012

    • Author(s)
      近藤小貴, 斎藤泉, Nic Jones
    • Organizer
      第18回日本遺伝子治療学会
    • Place of Presentation
      熊本
    • Related Report
      2012 Research-status Report
  • [Presentation] MicroRNAs as possible targets of MAPK signaling pathway to suppress oncogenic Ras-mediated tumorigenesis2012

    • Author(s)
      近藤小貴、鐘ヶ江裕美、斎藤泉
    • Organizer
      第71回日本癌学会
    • Place of Presentation
      札幌
    • Related Report
      2012 Research-status Report
  • [Presentation] A role of microRNAs for sensitization to cisplatin in ovarian cancer cell lines2012

    • Author(s)
      Saki Kondo, Yumi Kanegae, Nic Jones, Izumu Saito
    • Organizer
      European Society of Gene and Cell Therapy meeting
    • Place of Presentation
      Versailles, France
    • Related Report
      2012 Research-status Report
  • [Presentation] 高力価VA RNAs欠失アデノウイルスベクター新規作成法の開発2012

    • Author(s)
      前川文、裴崢、近藤小貴、鐘ヶ江裕美、斎藤泉
    • Organizer
      第60回日本ウイルス学会
    • Place of Presentation
      大阪
    • Related Report
      2012 Research-status Report
  • [Presentation] VA RNA欠失型アデノウイルスベクターを用いたC型肝炎治療法の開発2012

    • Author(s)
      裴崢、史国利、近藤小貴、伊藤昌彦、鐘ヶ江裕美、鈴木哲朗、斎藤泉
    • Organizer
      第60回日本ウイルス学会
    • Place of Presentation
      大阪
    • Related Report
      2012 Research-status Report
  • [Presentation] 第一世代アデノウイルスベクターにおける異なる目的遺伝子挿入部位による発現効率の比較検討2012

    • Author(s)
      鈴木まりこ、前川文、近藤小貴、鐘ヶ江裕美、斎藤泉
    • Organizer
      第60回日本ウイルス学会
    • Place of Presentation
      大阪
    • Related Report
      2012 Research-status Report
  • [Presentation] 高力価VA RNAs欠失アデノウイルスベクター新規作成法の開発2012

    • Author(s)
      前川文、裴崢、鈴木まりこ、近藤小貴、鐘ヶ江裕美、斎藤泉
    • Organizer
      第35回日本分子生物学会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] アデノウイルスベクターから発現するVA RNAがshRNAに影響を与えるか2012

    • Author(s)
      裴崢、史国利、近藤小貴、伊藤昌彦、鈴木哲朗、斎藤泉、鐘ヶ江裕美
    • Organizer
      第35回日本分子生物学会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Book] 実はもっと簡単で使いやすいアデノウイルスベクター(第32巻)2014

    • Author(s)
      近藤小貴, 他
    • Publisher
      羊土社
    • Related Report
      2013 Final Research Report
  • [Book] 実験医学2014

    • Author(s)
      近藤小貴、裴 崢、斎藤 泉、鐘ヶ江裕美
    • Total Pages
      6
    • Publisher
      羊土社
    • Related Report
      2013 Annual Research Report
  • [Book] アデノウイルスベクターの最近の進展:VA欠失ベクターを中心に, 日本ウイルス学会 (第63巻)2013

    • Author(s)
      近藤小貴, 他
    • Related Report
      2013 Final Research Report
  • [Book] ウイルス2013

    • Author(s)
      近藤小貴、前川 文、斎藤 泉、鐘ヶ江裕美
    • Total Pages
      14
    • Publisher
      日本ウイルス学会
    • Related Report
      2013 Annual Research Report

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Published: 2013-05-31   Modified: 2019-07-29  

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