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Gene Therapy Using rAAV Vector Against Hematological Disorders : From Basic Science To Clinical Application.

Research Project

Project/Area Number 09671105
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionNagoya University

Principal Investigator

TANIMOTO Mitsune  School of Medicine, Nagoya University Assistant Professor, 医学部, 講師 (10240805)

Co-Investigator(Kenkyū-buntansha) IIJIMA Narikazu  School of Medicine, Medical Staff, 医学部, 医員
KOUNO Akio  School of Medicine, Medical Staff, 医学部, 医員
唐渡 雅行  名古屋大学, 医学部, 医員
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1998: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1997: ¥2,500,000 (Direct Cost: ¥2,500,000)
Keywordsgene therapy / adeno associate virus / gene transduction / hematopoetic cell / cell therapy / cell culture / GVL effect / hematopoietic neoplasms / 造血幹細胞移植 / GLV効果 / ドナーリンパ球輸注 / リコンビナント / AAV
Research Abstract

Adeno associated virus (AAV) has been thought to be the promising vector for gene therapy because of its wide range of human tissues and low toxicity. We have recently initiated the study of rAAV for hematopoietic cells. Preliminary results revealed that the transduction efficiencies assessed by colony formation assay employing NeoR gene into various cell lines, were CML->AML->ALL-derived cell lines by log differences. Present study was performed using peripheral T cell as a target tissue. After purification and concentration of rAAV, 27% efficiency was observed in CML line at an MOI of 7 and a linear relationship between MOI and efficiency was confirmed, suggesting that this syatem may be useful for gene transduction into leukemia cells. Integration of the NeoR gene into the host genome was assessed by Southern blotting, that revealed various sizes of DNA fragments. A fluorescent in situ hybridization (FISH) analysis was perfomed on 11 clones, in all of which the NeoR gene was integrated out of chromosome 19. In five clones, chromosome painting probes showed that the integration sites were chromosome 1q, 2q, 2q, 11p, 12p and l3q.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Iida H,Towatari M,Tanimoto M et al: "Overexpression of cyclin E in acute myelogenous leukemia" Blood. 90. 3707-13 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Abe A,Emi N,Tanimoto M et al: "Fusion of the platelet-derived growth factor receptor beta to a novel gene CEV14 in acute myelogenous leukemia after clonal evolution." Blood. 90. 4271-7 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Iijima N,Miyamura K,Itou T,Tanimoto M et al: "Functional expression of Fas(CD95)in acute myeloid leukemia cells in the context of CD34 and CD38 expression: possible correlation with sensitivity to chemotherapy" Blood. 90. 4901-9 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Itou T,Miyamura K,Abe A,Emi N,Tanimoto M et al: "Recombinant adeno-associated virus-mediated gene transfer into human leukemia cell lines" Int J Hematol. 67. 27-35 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kohno A,Emi N,Kasai M,Tanimoto M,Saito H: "Semliki Forest virus-based DNA expression vector: transient protein production followed by cell death." Gene Ther. 5. 415-8 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Iida H,Towatari M,Tanimoto M et al: "Overexpression of cyclin E in acute myelogenous leukemia" Blood. 90. 3707-3713 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Abe A,Emi N,Tanimoto M et al: "Fusion of the platelet-derived growth factor receptor beta to a novel gene CEV14 in acute myelogenous leukemia after clonal evolution." Blood. 90. 4271-4277 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Iijima N,Miyamura K,Itou T,Tanimoto M et al.: "Functional expression of Fas (CD95) in acute myeloid leukemia cells in the context of CD34 and CD38 expression : possible correlation with sensitivity to chemotherapy." Blood. 90. 4901-4909 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Itou T,Miyamura K,Abe A,Emi N,Tanimoto M et al.: "Recombinant adeno-associated virus-mediated gene transfer into human leukemia cell lines" Int J Hematol. 67. 27-35 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kohno A,Emi N,Kasai M,Tanimoto M,Saito H: "Semliki Forest virus-based DNA expression vector : transient protein production followed by cell death." Gene Ther. 5. 415-418 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Iida H, Towatari M, Tanimoto M et al.: "Overexpression of cyclin E in acute myclogeous leukemia" Blood. 90. 3707-13 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] A be A, Emi N, Tanimoto M et al.: "Fusion of the platelet-dervied growth factor receptor beta to a novel gene CEV14 in acute myelogenous leukemia after clonal evolution." Blood. 90. 4271-7 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Iijima N, Miyamura K, Itou T, Tanimoto M et al.: "Functional expression of Fas (CD95) in acute myeloid leukemia cells in the context of CD34 and CD38 expression : possible correlation with sensitivity to chemotherapy" Blood. 90. 4901-9 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Itou T, Miyamura K, Abe A, Emi N, Tanimoto M et al: "Recombinant adeno-associated virus-mediated gene transfer into human leukemia cell lines" Int J Hematol. 67. 27-35 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kohno A, Emi N, Kasai M, Tanimoto M, Saito H: "Semliki Forest virus-based DNA expression vector : transient protein production followed by cell death." Gene Ther. 5. 415-8 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Abe A., Emi N., Tanimoto M.et al.: "Fusion of the Platelet-Derived Growth Facter Recepter beta to a Novel Gene CEV14 in Acute Myelogenous Leukemia After Clonal Evolution" Blood. 90. 4271-4277 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Iijima N.Miyamura K., Tanimoto M. et al.: "Functional Expression of Fas (CD95) in Acute Myeloid Leukemia Cells in the Context of CD34 and CD38 Expression : Possible Correlation With Sensitivity to Chemotheapy" Blood. 90. 4901-4909 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Iida H.Towatari M., Tanimoto M. et al.: "Overexpression of Cyclin E in Acute Myelogenous Leukemia" Blood. 90. 3707-3713 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Towatari M., Iida H., Tanimoto M, et al: "Costitutive Activation of Mitogen-Activated Protein Kinase Pathway in Acute Leukemia Cells" Leukemia. 11. 479-484 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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