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Gene Therapy with Glioma-specific gene expression adenovirus vector

Research Project

Project/Area Number 11671352
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionGunma University

Principal Investigator

KURIHARA Hideyuki  Gunma Univ.Sch.of Med, Dept.of Neurosurgery Assistant professor, 医学部, 講師 (30261853)

Co-Investigator(Kenkyū-buntansha) TAKEUCHI Toshiyuki  Gunma Univ.sch.of Med, Molecular Medicine, Prefessor, 生体調節研究所, 教授 (00109977)
田村 勝  群馬大学, 医学部, 助教授 (50163697)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsgene therapy / glioma / nestin / adenovirus vector / selective gene expression / p53 / targeting
Research Abstract

Glioma is one of the most common primary brain tumors, and develops invasively in the normal brain tissues. Therefore, in the gene therapy of glioma using suicide gene, such as p53, glioma-specific gene expression is a prerequisite for prevention against the normal brain injuly. We have developed a glioma-specific adenoviral gene expression vector using a "nestin" regulatory element. Nestin is a central nervous system(CNS)progenitor cell-specific intermediate filament, and the incidence of nestin expression correlates well with malignancy of glioma. We have constructed glioma-specific "regulator" recombinant adenovirus vector, Ax2INPNCre, which contains the site-specific recombinase Cre under the control of the rat nestin regulatory element 2iNP.Recently, we elucidated this double-infection method using the nestin regulatory element is applicable for glioma-specific gene therapy by the effecter virus using lacZ gene. For the treatment of glioma, we have constructed AxCALNLNp53K, which activate the p53 gene under the control of a potent CAG promoter by the Cre-producing adenoviruses.
For assessing the cell toxicity of this adenoviral system, we used two p53 mutated human glioma cell line, U251, which highly express nestin gene, and and T98, which little express nestin gene. Co-transfection of Ax2iNPCre and AxCALNLp53K induced the cell death to U251 within three days after the infection, but not to T98.
Co-transfection of AxCACre(control vector which highly express Cre in almost eucaryotic cells, and AxCALNLp53K induced the cell death to T98. Thus, nestin positive cell selective induction of cell death was achieved by this double infection therapy.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (2 results)

All Other

All Publications (2 results)

  • [Publications] Kurihara H, et al: "Glioma/Glioblastoma-specific adenovirus gene expression using the nestin gene regultor"Gene Therepy. 7. 686-693 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kurihara H, Zama A, Tamura M, Takeda J Sasaki T and Takeuchi T: "Glioma/Glioblastoma-specific adenovirus gene expression using the nestin gene regultor"Gene Therepy. 7. 686-693 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary

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Published: 1999-04-01   Modified: 2016-04-21  

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