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Improvement of helper-dependent adenovirus vector not only increasing gene expression but also cell/tissue specificity

Research Project

Project/Area Number 23590377
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Human genetics
Research InstitutionThe University of Tokyo

Principal Investigator

KANEGAE Yumi  東京大学, 医科学研究所, 助教 (80251453)

Co-Investigator(Renkei-kenkyūsha) SAITO Izumu  東京大学, 医科学研究所, 教授 (70158913)
Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords遺伝子治療 / アデノウイルスベクター / 細胞特異性
Research Abstract

The helper-dependent adenovirus vector (HD-AdV) is attractive tool for gene therapy, specially, genetic disease, because of its low-inflammation. However, it was reported that the purpose gene expression efficiency is lower than E1-substituted AdV. In this study, we determined the useful stuffer region and demonstrated an only 0.3kb DNA region near the rightend of the virus genome played an important role for efficient gene expression. And we showed that this region did not code any protein and enhancer.
We also developed a construction method of "cell/tissue-specific HD-AdV", which contains a switch unit carrying Cre gene expressed by cell/tissue-specific promoter and a target unit bearing purpose gene expression unit regulated by Cre. We chose the TH promoter for the cell/tissue-specific promoter and GFP for purpose gene. Finally, we succeeded in the construction and detected the dopamine neuron specific expression by this vector.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (53 results)

All 2014 2013 2012 2011

All Journal Article (22 results) (of which Peer Reviewed: 12 results) Presentation (25 results) Book (4 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] Efficient production of adenovirus vector lacking genes of virus-associated RNAs that disturb celluar RNAi machinery2013

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

      Scientific Reports

      Volume: 3 Pages: 1136-1136

    • Related Report
      2013 Final Research Report
  • [Journal Article] Adenovius vectors lacking virus-associated RNA expression enhance shRNA atctivity to suppress hepatitis C virus replication2013

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

      Scientific Rep.

      Volume: 3 Pages: 3575-3575

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

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

      Scientific Report

      Volume: 3 Pages: 3575-3575

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efficient production of adenovirus vector lacking genes of virus-associated RNAs that disturb celluar 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 Reports

      Volume: 39

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Trans-complemented hepatitis C virus particles as a versatile tool for study of virus assembly and infection2012

    • Author(s)
      Suzuki R, Saito K, Kato T, Shirakura M, Akazawa D, Ishii K, Aizaki H, Kanegae Y, Matsuura Y, Saito I, Wakita T, Suzuki T
    • Journal Title

      Virology

      Volume: 432 Pages: 29-38

    • Related Report
      2013 Final Research Report
  • [Journal Article] Influence of loxP insertion upstream of the cis-acting packaging domain on adenovirus packaging efficiency2012

    • Author(s)
      Kanegae Y, Ishimura M, Kondo S, Saito I
    • Journal Title

      Microbiol Immunol

      Pages: 447-455

    • NAID

      40019336430

    • Related Report
      2013 Final Research Report
  • [Journal Article] Copy number of adenoviral vector genome transduced into target cells can be measured using quantitative PCR : Application to vector titration2012

    • Author(s)
      Pei, Z, Kondo S, Kanegae Y, Saito, I
    • Journal Title

      BBRC

      Volume: 417 Pages: 945-950

    • Related Report
      2013 Final Research Report
  • [Journal Article] Trans-complemented hepatitis C virus particles as a versatile tool for study of virus assembly and infection.2012

    • Author(s)
      Suzuki R., Saito K., Kato T., Shirakura M., Akazawa D., Ishii K., Aizaki H., Kanegae Y., Matsuura Y., Saito I., Wakita T. and Suzuki T.
    • Journal Title

      Virology

      Volume: 432 Pages: 29-38

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Copy number of adenoviral vector genome transduced into target cells can be measured using quantitative PCR: application to vector titration.2012

    • Author(s)
      Pei Z., Kondo S., Kanegae Y. and Saito I.
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 417 Pages: 945-950

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Influence of loxP insertion upstream of the cis-acting packaging domain on adenovirus packaging efficiency.2012

    • Author(s)
      Kanegae Y., Ishimura M., Kondo S., and Saito I.
    • Journal Title

      Microbiol Immunol

      Volume: 56 Pages: 447-455

    • NAID

      40019336430

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Conditional gene expression in hepatitis C virus transgenic mice without induction if severe liver injury using a non-inflammatory Cre-expressing adenovirus2011

    • Author(s)
      Chiyo T, Sekiguchi S, Hayashi M, Tobita Y, Kanegae Y, Saito I, Kohara M
    • Journal Title

      Virus Res

      Volume: 160 Pages: 89-97

    • Related Report
      2013 Final Research Report
  • [Journal Article] Comparison of efficiency between FLPe and Cre for recombinase-mediated cassette exchange (RMCE) in vitro and in adenovirus vector production2011

    • Author(s)
      Takata Y. Kondo S, Goda N, Kanegae Y, Saito I
    • Journal Title

      Genes Cells

      Volume: 16 Pages: 765-777

    • Related Report
      2013 Final Research Report
  • [Journal Article] High-level expression by tissue/cancer-specific promoter with strict specificity using a single adenoviral vector2011

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

      Nucleic Acids Res

      Volume: 39

    • Related Report
      2013 Final Research Report
  • [Journal Article] Keratinocyte growth factor gene transduction ameliorates pulmonary fibrosis induced by bleomycin inmice2011

    • Author(s)
      Sakamoto S, Yazawa T, Baba Y, Sato H, Kanegae Y, Hirai T, Saito I, Goto T, Kurahashi K
    • Journal Title

      Am. J. Respir. Cell Molec. Biol

      Pages: 489-497

    • Related Report
      2013 Final Research Report
  • [Journal Article] BavA-mediated adherence is a potentiator of the Helicobacter pylori type IV secretion systemactivity2011

    • Author(s)
      Ishijima N, Suzuki M, Acida H, Ichikawa Y, Kanegae Y, Saito I, Boren T, Haas R, Sasakawa Cand Mimuro H
    • Journal Title

      J. Biol. Chem

      Pages: 25256-25264

    • Related Report
      2013 Final Research Report
  • [Journal Article] Keratinocyte growth factor gene transduction ameliorates pulmonary fibrosis induced by bleomycin in mice.2011

    • Author(s)
      Sakamoto S, Yazawa T, Baba Y, Sato H, Kanegae Y, Hirai T, Saito I, Goto T and Kurahashi K.
    • Journal Title

      Am. J. Respir. Cell Molec. Biol.

      Volume: 45 Pages: 489-497

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Conditional gene expression in hepatitis C virus transgenic mice without induction of severe liver injury using a non-inflammatory Cre-expressing adenovirus.2011

    • Author(s)
      Chiyo T, Sekiguchi S, Hayashi M, Tobita Y, Kanegae Y, Saito I and Kohara M.
    • Journal Title

      Virus Res.

      Volume: 160 Pages: 89-97

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] BavA-mediated adherence is a potentiator of the Helicobacter pylori type IV secretion system activity.2011

    • Author(s)
      Ishijima N, Suzuki M, Acida H, Ichikawa Y, Kanegae Y, Saito I, Boren T, Haas R, Sasakawa C and Mimuro H.
    • Journal Title

      J. Biol. Chem.

      Volume: 286 Pages: 25256-25264

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Comparison of efficiency between FLPe and Cre for recombinase-mediated cassette exchange (RMCE) in vitro and in adenovirus vector production.2011

    • Author(s)
      Takata Y, Kondo S, Goda N, Kanegae Y and Saito I.
    • Journal Title

      Genes Cells

      Volume: 16 Pages: 765-777

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] opy number of adenoviral vector genome transduced into target cells can be measured using quantitative PCR: application to vector titration.2011

    • Author(s)
      Pei Z, Kondo S, Kanegae Y and Saito I.
    • Journal Title

      Biochem. Biophs. Res. Commun.

      Volume: 417 Pages: 945-950

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] 2) High-level expression by tissue/cancer-specific promoter with strict specificity using a single adenoviral vector.2011

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

      Nucleic Acids Res.

      Volume: 39

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [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
    • Related Report
      2013 Final Research Report
  • [Presentation] Therapeutic strategy of HBV using VA-deleted adenovirus vectors dually expressing shRNA and interferon2013

    • Author(s)
      Pei Z, Maekawa A, Suzuki M, Kanegae Y, Kondo S, Saito I
    • Organizer
      2013 International Meeting on Molecular Biology of Hepatitis B viruses
    • Place of Presentation
      Fudan University, Shanghai
    • Related Report
      2013 Final Research Report
  • [Presentation] Dual-safe adenovirus vector lacking virus-associated RNA genes enhanced shRNA activity2013

    • Author(s)
      Kanegae Y, Maekawa A, Pei Z, Suzuki M, Kondo S, Saito I
    • Organizer
      The 21th European Society of Gene and Cell Therapy collaborative Congress
    • Place of Presentation
      Madrid
    • Related Report
      2013 Final Research Report
  • [Presentation] First-generation adenovirus vector expresses viral-associated (VA) RNAs that disturb cellular gene expressions2013

    • Author(s)
      Kondo S, Maekawa A, Suzuki M, Kanegae Y, Saito I
    • Organizer
      The 21th European Society of Gene and Cell Therapy collaborative Congress
    • Place of Presentation
      Madrid
    • Related Report
      2013 Final 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)
      Maekawa A, Pei Z, Suzuki M, Kondo S, Saito I
    • Organizer
      The European Society of Gene and Cell Therapy 2013 Annual Meeting, Palacio Municipal de Congresos
    • Place of Presentation
      Madrid
    • Related Report
      2013 Final 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, 鈴木まりこ, 鐘ヶ江裕美
    • Organizer
      第61回日本ウイルス学会学術集会
    • Place of Presentation
      神戸
    • Related Report
      2013 Final 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
    • Organizer
      第61回日本ウイルス学会学術集会
    • Place of Presentation
      神戸
    • Related Report
      2013 Final 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
    • Related Report
      2013 Final 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
    • Related Report
      2013 Final 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の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
    • 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] Dual-safe adenovirus vector lacking virus-associated RNA genes enhanced shRNA activity.2013

    • Author(s)
      Kanegae Y, Maekawa A, Pei Z, Suzuki M, Kondo S, Saito I.
    • Organizer
      The 21th European Society of Gene and Cell Therapy collaborative Congress 2013
    • Place of Presentation
      Palacio Municipal de Congresos de Madrid, Spain
    • Related Report
      2013 Annual Research Report
  • [Presentation] First-generation adenovirus vector expresses viral-associated (VA) RNAs that disturb cellular gene expressions.2013

    • Author(s)
      Kondo S, Maekawa A, Suzuki M, Kanegae Y, Saito I.
    • Organizer
      The 21th European Society of Gene and Cell Therapy collaborative Congress 2013
    • Place of Presentation
      Palacio Municipal de Congresos de 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、鈴木 まりこ、鐘ヶ江 裕美
    • 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
    • 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
      国際会議場(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の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
      国際会議場(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
      国際会議場(神戸)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 高力価VA RNAs欠失アデノウイルスベクター新規作製法の開発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学術総会
    • Place of Presentation
      大阪
    • Related Report
      2013 Final Research 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学術総会
    • Place of Presentation
      大阪
    • Related Report
      2013 Final Research 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35回日本分子生物学会
    • Place of Presentation
      福岡
    • Related Report
      2013 Final Research 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製法の開発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
      2013 Final Research 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
      2013 Final Research 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製法の開発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
  • [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(実験医学, 第32巻)2014

    • Author(s)
      近藤小貴, 裴崢, 斎藤泉, 鐘ヶ江裕美
    • 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(第63巻)2013

    • Author(s)
      近藤小貴, 前川文, 斎藤泉, 鐘ヶ江裕美
    • Publisher
      日本ウイルス学会
    • 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
  • [Patent(Industrial Property Rights)] VA遺伝子破壊アデノウイルスベクターおよびそれを調製するための前駆体ベクター2012

    • Inventor(s)
      鐘ヶ江 裕美, 斎藤 泉
    • Industrial Property Rights Holder
      鐘ヶ江 裕美, 斎藤 泉
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2012-213069
    • Filing Date
      2012-09-26
    • Related Report
      2013 Final Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] VA遺伝子破壊アデノウイルスベクターおよびそれを調製するための前駆体ベクター2012

    • Inventor(s)
      鐘ヶ江裕美、斎藤泉
    • Industrial Property Rights Holder
      鐘ヶ江裕美、斎藤泉
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2012-213069
    • Filing Date
      2012-09-26
    • Related Report
      2012 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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