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Establishment of Baboon envelope pseudotyped LV vector system to maintain the stemness in stem cell gene therapy.

Research Project

Project/Area Number 15K09676
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research InstitutionNational Center for Child Health and Development

Principal Investigator

Uchiyama Toru  国立研究開発法人国立成育医療研究センター, 成育遺伝研究部, 室長 (10436107)

Research Collaborator Minegishi Tomoko  
Akiba Yumi  
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsレンチウイルスベクター / 造血幹細胞遺伝子治療 / 幹細胞性 / ヒヒ内在性レトロウイルス / 遺伝子治療 / BaEV / ヒト造血幹細胞 / baboon envelope / 安定ウイルス産生細胞株 / ウイルス安定産生細胞株
Outline of Final Research Achievements

An envelope protein of Baboon endogenous retrovirus (BaEV env) can efficiently package the lentivirus (LV) without any cytotoxicity, and we used BaEV env to make the stable packaging cell line for LV vector. LV gag-pol genes encoding structural proteins and rev regulatory gene were transferred into 293T cells to make 293LVgpr cells. Resultant cells expressed gag-pol and rev, and could make the lentivirus particle by the transfection of vector and any kind of envelope plasmids. To make the stable packaging cell line, we then transduce 293LVgpr cells with self-inactivating retroviral vector containing BaEV env. Transduced cells, however, could not produce high titer of LV by the transfection of vector plasmid, because the expression level of BaEV env is not sufficient. We now try to increase the copy number of BaEV env in 293LVgpr cells to increase its expression.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (24 results)

All 2018 2017 2016 2015

All Journal Article (8 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 8 results,  Open Access: 3 results,  Acknowledgement Compliant: 3 results) Presentation (14 results) (of which Int'l Joint Research: 1 results,  Invited: 5 results) Book (2 results)

  • [Journal Article] Somatic MECOM mosaicism in a patient with congenital bone marrow failure without a radial abnormality2018

    • Author(s)
      Osumi Tomoo、Tsujimoto Shin-ichi、Nakabayashi Kazuhiko、Taniguchi Maki、Shirai Ryota、Yoshida Masanori、Uchiyama Toru、Nagasawa Junko、Goyama Susumu、Yoshioka Takako、Tomizawa Daisuke、Kurokawa Mineo、Matsubara Yoichi、Kiyokawa Nobutaka、Matsumoto Kimikazu、Hata Kenichiro、Kato Motohiro
    • Journal Title

      Pediatric Blood & Cancer

      Volume: 65 Issue: 6

    • DOI

      10.1002/pbc.26959

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fecal calprotectin rise in chronic granulomatous disease.2017

    • Author(s)
      Nakazawa Y, Kawai T, Arai K, Tamura E, Uchiyama T, Onodera M
    • Journal Title

      J. Clin. Immunol.

      Volume: 37 Pages: 741-743

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ingle cell-based vector tracing in patients with ADA-SCID treated with stem cell gene therapy.2017

    • Author(s)
      Igarashi Y, Uchiyama T, Minegishi T, Takahashi S, Watanabe N, Kawai T, Yamada M, Ariga T, Onodera M
    • Journal Title

      Mol. Ther. Methods. Clin. Dev

      Volume: 6 Pages: 8-16

    • DOI

      10.1016/j.omtm.2017.05.005

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Persistent Impairment of T-Cell Regeneration in a Patient with Activated PI3K δ Syndrome2017

    • Author(s)
      Goto F, Uchiyama T, Nakazawa Y, Imai K, Kawai T, Onodera M
    • Journal Title

      J Clin Immunol

      Volume: 37 Issue: 4 Pages: 347-350

    • DOI

      10.1007/s10875-017-0393-7

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Blastic transformation of juvenile myelomonocytic leukemia caused by the copy number gain of oncogenic KRAS.2017

    • Author(s)
      Osumi T, Kato M, Ouchi-Uchiyama M, Tomizawa D, Kataoka K, Fujii Y, Seki M, Takita J, Ogawa S, Uchiyama T, Ohki K, Kiyokawa N.
    • Journal Title

      Pediatr Blood Cancer. Pediatr Blood Cancer.

      Volume: 64(9) Issue: 9

    • DOI

      10.1002/pbc.26496

    • Related Report
      2017 Annual Research Report 2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The long terminal repeat negative control region is a critical element for insertion oncogenesis after gene transfer into hematopoietic progenys with Moloney murine leukemia viral vectors.2016

    • Author(s)
      Ikawa Y, Uchiyama T, Jagadeesh GJ, Candotti F
    • Journal Title

      Gene therapy

      Volume: 23 Issue: 11 Pages: 815-818

    • DOI

      10.1038/gt.2016.51

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Effects of enzyme replacement therapy on immune function in ADA deficiency patient2015

    • Author(s)
      Nakazawa Y, Kawai T, Uchiyama T, Goto F, Watanabe N, Maekawa T, Ishigro A, Okuyama, T, Otsu M, Yamada M, Hershfield MS, Ariga T, Onodera M
    • Journal Title

      Clinical Immunology

      Volume: 161 Issue: 2 Pages: 391-393

    • DOI

      10.1016/j.clim.2015.06.011

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Severe and Rapid Progression in Very Early-Onset Chronic Granulomatous Disease-Associated Colitis.2015

    • Author(s)
      Kawai T, Arai K, Harayama S, Nakazawa Y, Goto F, Maekawa T, Tamura E, Uchiyama T, Onodera M
    • Journal Title

      Journal if Clinical Immunology

      Volume: 35 Issue: 6 Pages: 583-588

    • DOI

      10.1007/s10875-015-0180-2

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Current status of hematopoietic stem cell gene therapy for Wiskott-Aldrich syndrome in Japan.2017

    • Author(s)
      Toru Uchiyama
    • Organizer
      The 7th International Collaboration Forum of Human Gene Therapy for Genetic Disease.
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] デノシンデアミナーゼ欠損症の従姉弟例2017

    • Author(s)
      内山 徹
    • Organizer
      第10回日本免疫不全症研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Progress in gene therapy for primary immunodeficiencies2017

    • Author(s)
      内山 徹
    • Organizer
      第23回日本遺伝子細胞治療学会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Current status of hematopoietic stem cell gene therapy for Wiskott-Aldrich syndrome in Japan2017

    • Author(s)
      Uchiyama T
    • Organizer
      The 7th International Collaboration Forum of Human Gene Therapy for Genetic Disease
    • Place of Presentation
      東京
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Selective pressure of vector-derived ADA in ADA-SCID patients treated with gene therapy2016

    • Author(s)
      内山徹、五十嵐友香、渡辺信之、高橋シリラット、中澤裕美子、河合利尚、後藤文洋、山田雅文、有賀正、小野寺雅史
    • Organizer
      第78回日本血液学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-13
    • Related Report
      2016 Research-status Report
  • [Presentation] 重症複合免疫不全症(SCID)の新生児スクリーニング2016

    • Author(s)
      後藤文洋、長田香代、峰岸知子、諸田沙織、中島英規、奥山虎之、河合利尚、小野寺雅史、内山徹
    • Organizer
      第43回日本マススクリーニング学会
    • Place of Presentation
      札幌
    • Year and Date
      2016-08-26
    • Related Report
      2016 Research-status Report
  • [Presentation] Hematopoietic stem cell gene therapy for Wiskott-Aldrich syndrome2016

    • Author(s)
      Uchiyama T
    • Organizer
      第22回日本遺伝子治療学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2016-07-28
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Single cell-based vector tracing in the patients treated with stem cell gene therapy2016

    • Author(s)
      Takahashi S, Igarashi Y, Uchiyama T, Onodera M.
    • Organizer
      第22回日本遺伝子治療学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2016-07-28
    • Related Report
      2016 Research-status Report
  • [Presentation] Hematopoietic stem cell gene therapy for Wiskott-Aldrich syndrome2016

    • Author(s)
      Toru Uchiyama, Satoshi Horino, Tkanori So, G Jayashree Jagadeesh, Naoto Ishii, Fabio Candotti
    • Organizer
      Japan Society of Gene and Cell Therapy, 22nd Annual Meeting
    • Place of Presentation
      Tokyo
    • Year and Date
      2016-07-28
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 乾燥ろ紙血を用いた原発性免疫不全症の新生児マススクリーニングパイロット研究2016

    • Author(s)
      河合利尚、内山徹、後藤文洋、中澤裕美子、小須賀基通、和田友香、塚本桂子、伊藤裕司、奥山虎之、小野寺雅史
    • Organizer
      第119回小児科学会学術集会
    • Place of Presentation
      札幌
    • Year and Date
      2016-05-13
    • Related Report
      2016 Research-status Report
  • [Presentation] Rapamycin controls lymph proliferation and restores functional T cells in Activated PI3Kd syndrome2015

    • Author(s)
      Uchiyama T
    • Organizer
      第77回日本血液学会学術集会
    • Place of Presentation
      金沢
    • Year and Date
      2015-10-16
    • Related Report
      2015 Research-status Report
  • [Presentation] A novel tracking system of transgene using droplet-based single cell PCR in hematopoietic stem cell gene therapy2015

    • Author(s)
      Igarashi Y, Uchiyama T, Wanatabe N, Nakazawa Y, Otsu M, Ariga T, Onodera M
    • Organizer
      European Society of Gene and Cell Therapy and Finnish Society of Gene therapy Collaborative Congress
    • Place of Presentation
      Helsinki, Finland
    • Year and Date
      2015-09-17
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Influence of virus production methods on genotoxic potential of gene transfer vectors2015

    • Author(s)
      Takahashi S, Uchiyama T, Onodera M
    • Organizer
      Japan Society of Gene Therapy, 21th Annual Meeting
    • Place of Presentation
      Osaka
    • Year and Date
      2015-07-24
    • Related Report
      2015 Research-status Report
  • [Presentation] Regulatory science of viral vector for gene therapy2015

    • Author(s)
      Igarashi Y, Uchiyama T, Uchida E, Onodera M
    • Organizer
      Japan Society of Gene Therapy, 21th Annual Meeting
    • Place of Presentation
      Osaka
    • Year and Date
      2015-07-24
    • Related Report
      2015 Research-status Report
  • [Book] 小児内科2017

    • Author(s)
      内山徹
    • Total Pages
      4
    • Publisher
      東京医学社
    • Related Report
      2017 Annual Research Report
  • [Book] 先端治療技術の実用化と開発戦略2017

    • Author(s)
      内山徹
    • Total Pages
      7
    • Publisher
      技術情報協会
    • ISBN
      9784861046506
    • Related Report
      2017 Annual Research Report

URL: 

Published: 2015-04-16   Modified: 2019-12-27  

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