• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Gene carrier system by means of alveolar macrophage to the lung : an attempt of gene therapy for lung diseases.

Research Project

Project/Area Number 09670601
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionChiba University School of Medicine

Principal Investigator

KURIYAMA Takayuki  Chiba University School of Medicine, Professor, 医学部, 教授 (20009723)

Co-Investigator(Kenkyū-buntansha) TAKIGUCHI Yuichi  Chiba University School of Medicine, Assistant, 医学部, 助手 (30272321)
KIMURA Hiroshi  Chiba University School of Medicine, Associate Professor, 医学部, 助教授 (20195374)
杉本 尚昭  千葉大学, 医学部・付属病院, 医員
大森 繁成  千葉大学, 医学部・付属病院, 医員
宮沢 裕  千葉大学, 医学部・付属病院, 医員
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1998: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1997: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsAlveolar Macrophage / Gene Vector / Gene Transfer / Gene Therapy / Fibroblast
Research Abstract

A novel gene delivery system to lung has been established in mice. The method employs intravenous injection of syngeneic viable cells that are transfected with a target gene in ex vivo.
In a series of preliminary studies, attempts of transfecting syngeneic alveolar macrophages with a reporter gene by means of non-viral methods, i.e. calcium-phosphate co-precipitation, electropolation and lipofectin have failed, In the next step, syngeneic fibroblasts instead of alveolar macrophages were utilized to reveal high efficacy of gene transfection. Eventually, a plasmid that had bacterial beta-galactosidase (beta-gal) gene under the control of a beta-actin promoter was transfected to an established Balb/c mouse derived fibroblast cell line, A3 1, by the calcium-phosphate co-precipitation method in vitro. The cells were propagated in vitro and administrated to syngeneic Balb/c mice by intra tracheal (I.T.) or intra venous (I.V.) method. After the administrations, each organ, induding lung, heart, kidney, liver, brain and spleen was removed from the sacrificed mice, and the beta-gal activity in the each organ was assessed by ELISA.A high level of beta -gal expression was observed in lung tissues, lasting as long as about two weeks, with a peak at 2 hours after the administration. Kinetic differences of the gene expression between I.T.and I.V.administration were comparatively evaluated. All other organs, except for hearts, showed no detectable expression after either I.T.or I.V.administration, when evaluated by ELISA and RT-PCR.Histological examinations with beta -gal staining showed identification and localization of the administrated cells those showed high expression of the introduced gene in the lung. Other histological examination with hematoxylin-eosin staining disclosed no significant lesions such as inflammation and fibrosis in the lungs.
In conclusion, this study demonstrated potential clinical capability and safety of this gene delivery system for lung diseases.

Report

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

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Takiguchi, Y.: "Cenomic structure and chromosomal assignment of the mouse Ku 70 gene" Genomics. 35. 129-135 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takiguchi, Y.: "Evaluation of metastatic ability at specific times during primary tumor grouwth ; a nonel, spontaneous metastasis assay" Clinical and Experimental Metastasis. 13. 184-190 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kamei, K. Kuriyama, T.: "Supprossion of candidacidal activity of human pulmonary alveolar macrophage with serum of cancer patients" J.Exp.clin. Cancer Res.11. 133-138 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takiguchi, Y.: "Genomic structure of the mouse apurinic/apyrimidinic endonuclease gene" mammalian genome. 5. 717-722 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takiguchi Y: "Genomic structure and chromosomal assignment of the mouse Ku 70 gene." Genomics. 35. 129-135 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takiguchi Y: "Evaluation of metastatic ability at specific times during primary tumor growth ; a novel, spontaneous metastasis assay." Clinical and Experimental Metastasis. 13. 184-190 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Kamei K,Kuriyama T: "Suppression of candidacidal activity of human pulmonary alveolar macrophage with serum of cancer patients." J.Exp.Clin.Cancer Res. 11. 133-138 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takiguchi Y: "Genomic structure of the mouse apurinic/apyrimidinic endonuclease gene." Mammalian genome. 5. 717-722 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takiguchi,Y.: "Genomic structure and chromosomal assignment of the mouse Ku 70 gene" Genomics. 35. 129-135 (1996)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takiguchi,Y.: "Evaluation of metastatic ability at specific times during primary tumor grouwth;a nonel,spontaneous metastasis assay" Clinical and Experimental Metastasis. 13. 184-190 (1995)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kamei,K. Kuriyama,T: "Suppression of candidacidal activity of human pulmonary alveolar macropha with serum of cancer patients" J.Exp.Clin.Cancer Res.11. 133-138 (1992)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takiguchi,Y.: "Genomic structure of the mouse apurinic/apyrimidinic endonuclease gene" mammalian genome. 5. 717-722 (1994)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takiguchi,Y: "Genomic structure and chnmosomal assignment of the mouse Ku 70 gene" Genomics. 35. 129-135 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takiguchi,Y: "Evalaution of metastatic ability at specific times during primary tumor growth:a novel,spontaneous metastasis assay" Clinical and Experimental Metastasis. 13. 184-190 (1995)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kamei,K., Kuriyama,T: "Suppression of candidacidal activity of human pulmonary alveolar macrophages with serum of cancer patients" J.Erp Clin Cancer Res.11. 133-138 (1992)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takiguchi,Y: "Genomic structure of the mouse apurinic/apyrimidnic endonuclease gene" Mammalian Genone. 5. 717-722 (1994)

    • Related Report
      1997 Annual Research Report

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi