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1998 Fiscal Year Final Research Report Summary

Basic Research of Gene Therapy for Joint Diseases

Research Project

Project/Area Number 09470320
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionKYOTO PREFECTURAL UNIVERSITY OF MEDICINE

Principal Investigator

KUBO Toshikazu  Kyoto Prefectural University of Medicine, Medical School, Associate Professor, 医学部, 助教授 (20178031)

Co-Investigator(Kenkyū-buntansha) TAKIGAWA Masaharu  Okayama University, Dental School, Professor, 歯学部, 教授 (20112063)
SAWADA Kouhei  Kyoto Prefectural University of Medicine, Medical School, Assistant, 医学部, 助手 (40264767)
Project Period (FY) 1997 – 1998
Keywordsgene therapy / adenovirus vector / guinea pig / in vivo / drug delivery system / TGF-betaI / joint
Research Abstract

We evaluated the in vivo applicability of adenovirus-mediated gene delivery in order to consider the feasibility of gene therapy for human joint diseases.
We directly injected vectors harbouring beta-galactosidase (beta-gal) or transforming growth factor (TGF)-beta1 gene into the joints of Hartley guinea pigs. Expressions of transduced beta-gal genes were examined by 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-gal) staining and reverse transcription- polymerase chain reaction (RT-PCR). The levels of TGF-beta1 which was delivered to the joint and then transferred to the joint fluid, were assessed by enzyme-linked immunosorbent assay (ELISA). LacZ expression was observed in almost the entire synovial tissues and in chondrocytes on the surface of degenerated cartilage. Un expected effects of the direct vector inj ection on the other organs were also examined, no expression of delivered gene was observed. Therefore, intraarticular direct injection would achieve gene delivery limited to the joint cavity, possibly eliminating unecessary systemic effects. TGF-beta1 levels in the joint fluid following the gene delivery had been significantly higher than the levels in the controls for 2 weeks.
Direct gene delivery into the joint cavity is realistic with the in vivo gene delivery method using adenovirus vector, and it would be clinically applicable.

  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Arai,Y.: "Adenovirus vector-mediated gene transduction to chondrocytes : In vitro evaluation of therapeutic efficacy of transforming growth factor-β1 and heat shock protein 70 gene transduction." The Journal of Rheumatology. 24(9). 1787-1795 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ikeda,T.: "Adenovirus mediated gene delivery to the joints of guinea pigs." The Journal of Rheumatology. 25(9). 1666-1673 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 久保 俊一: "アデノウイルスベクターによる軟骨細胞に対する遺伝子導入法の検討" Academia. 171. 16-22 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 久保 俊一: "関節軟骨修復に対する遺伝子治療" 骨・関節・靭帯. 10(11). 1339-1347 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 久保 俊一: "軟骨修復とサイトカイン -遺伝子導入を用いて-" 整形・災害外科. 41(1). 37-44 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 久保 俊一: "アデノウイルスベクターを用いた遺伝子治療" 整形・災害外科. 41(9). 1087-1091 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Arai, Y.: "Adenovirus vector-mediated gene transduction to chondrocytes : In vitro evaluation of therapeutic efficacy of transforming growth factor-beta1 and heat shock protein 70 gene transduction" The Journal of Rheumatology. 24 (9). 1787-1795 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ikeda, T.: "Adenovirus mediated gene delivery to the joints of guinea pigs" The Journal of Rheumatology. 25 (9). 1666-1673 (1998)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-12-08  

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