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Development of gene therapy for progressive renal diseases by ribozyme

Research Project

Project/Area Number 15590863
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Kidney internal medicine
Research InstitutionNihon University

Principal Investigator

FUKUDA Noboru  Nihon University, School of Medicine, Instructor, 医学部, 講師 (40267050)

Co-Investigator(Kenkyū-buntansha) MATSUMOTO Koichi  Nihon University, School of Medicine, Professor, 医学部, 教授 (00125064)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsPDGF A-chain / TGF-b1 / ribozyme / adeno virus / kidney disease / TGF-β1
Research Abstract

To develop ribozyme therapy for progressive renal diseases, we designed and synthesized the nucleic acid resistant DNA/RNA chimeric ribozyme targeting PDGF A-chain and TGF-b1 by DNA/RNA synthesizer. In addition, we also obtained the recombinant ribozyme targeting PDGF A-chain and TGF-b1 adeno virus vector. FITC-labeled DNA/RNA chimeric ribozymes were considerably delivered into cultured mesangial cells with zelatin delivery reagent. The ribozymes significantly inhibited expression of PDGF A-chain and TGF-b1 mRNA in mesangial cells in vitro.
Based on the in vitro experimental results, we investigated in vivo delivery and effects of the DNA/RNA chimeric ribozyme targeting PDGF A-chain and TGF-b1 on progressive renel diseases in Dahl-salt sensitive rats. FITC-labeled DNA/RNA chimeric ribozymes injected intravenously were sufficinatly delivered into gromeruli and nephrotubulus in Dahl-salt sensitive rats. The DNA/RNA chimeric ribozymes with the zelatin delivery reagent and the recombinant ribozymes significantly inhibited expressions of PDGF A-chain and TGF-b1 mRNAs and proteins in renal cortex, and decreased urinary protein excressions to half levels. Intra venous injections of excess amount of the DNA/RNA chimeric ribozymes with the zelatin delivery reagent and the recombinant ribozymes did not induce tissue damages in spleen, bone marrow, testis, kideney and heart, indicating that safety of the ribozyme treatments in vivo.
These results suggest that the the DNA/RNA chimeric ribozymes with the zelatin delivery reagent and the recombinant ribozymes targeting PDGF A-chain and TGF-b1 will be feasible gene therapy for the progressive renal diseases.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (39 results)

All 2005 2004 2003 Other

All Journal Article (26 results) Book (4 results) Patent(Industrial Property Rights) (2 results) Publications (7 results)

  • [Journal Article] Effects of DNA-RNA chimeric ribozyme targeting TGF- β1 on growth of human gingival fibroblast2005

    • Author(s)
      Yusa J, Fukuda N, et al.
    • Journal Title

      Journal of Periodontology (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Synthetic pyrrole-imidazole polyamide inhibits human transforming growth factor- β1 gene expression2005

    • Author(s)
      Lai Y, Fukuda N, et al.
    • Journal Title

      Journal of Pharmacology Experimental Therapeutics (submitting)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Chimeric DNA-RNA hammerhead ribozyme targeting TGF- β1 mRNA efficiently ameliorated renal injury in hypertensive rats2005

    • Author(s)
      Tahira Y, Fukuda N, et al.
    • Journal Title

      Hypertension (submitting)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effects of DNA-RNA chimeric ribozyme targeting TGF-b1 on growth of human gingival fibroblast.2005

    • Author(s)
      Yusa J, Fukuda N, Sato S, Kamoi K, Mugishima H.
    • Journal Title

      J.Periodontor (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Synthetic pyrrole-imidazole polyamide inhibits human transforming growth factor-b1 gene expression.2005

    • Author(s)
      Lai Y-M, Fukuda N, Ueno T, Kishioka H, Matsuda Y, Saito S, Matsumoto K, Saito T, Iida H, Ayame H, Bando T, Sugiyama H, Mugishima H, Kim S-J.
    • Journal Title

      J Pharmacol Exp Therap (submitting)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Chimeric DNA-RNA hammerhead ribozyme targeting TGF-2_1 mRNA efficiently ameliorated renal injury in hypertensive rats.2005

    • Author(s)
      Tahira Y, Fukuda N, Endo M, Suzuki R, Takagi H, Ikeda Y, Ueno T, Matsuda H, Saito S, Matsumoto K, Mugishima H.
    • Journal Title

      Hypertension (submitting)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effects of DNA-RNA chimeric ribozyme targeting TGF-β1 on growth of human gingival fibroblasts.2005

    • Author(s)
      Yusa J, Fukuda N, et al.
    • Journal Title

      Journal of Periodontology (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Chimeric DNA-RNA hammerhead ribozyme targeting TGF-β1 mRNA inhibits neointima formation in rat carotid artery after ballooninjury2004

    • Author(s)
      Ando H, Fukuda N, et al.
    • Journal Title

      European Journal of Pharmacology 483

      Pages: 207-214

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Adenovirus-encoded hammerhead ribozyme to PDGF A-chain mRNA inhibits neointima formation after arterial injury2004

    • Author(s)
      Lin Z-H, Fukuda N, et al.
    • Journal Title

      Vournal of Vascular Research 41

      Pages: 305-313

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Presence and prospect of gene therapy for ischemic heart diseases2004

    • Author(s)
      Fukuda N, Saito S
    • Journal Title

      Nihon University Journal of Medicine 46

      Pages: 91-105

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Chimeric DNA-RNA hammerhead ribozyme targeting TGF-β1 mRNA inhibits neointima formation in rat carotid artery after balloon injury.2004

    • Author(s)
      Ando H, Fukuda N, Kotani M, Yokoyama S, Kunimoto S, Matsumoto K, Saito S, Kanmatsuse K, Mugishima H.
    • Journal Title

      Eur J Pharmacol 483

      Pages: 207-214

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Adenovirus-encoded hammerhead ribozyme to PDGF A-chain mRNA inhibits neointima formation after arterial injury.2004

    • Author(s)
      LinZ-H, Fukuda N, Suzuki R, Takagi H, Ikeda Y, Saito S, Matsumoto K, Kanmatsuse K, Mugishima H.
    • Journal Title

      J Vasc Res 41

      Pages: 305-313

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Presence and prospect of gene therapy for ischemic heart diseases.2004

    • Author(s)
      Fukuda N, Saito S.
    • Journal Title

      Nihon Univ.J.Med. 46

      Pages: 91-105

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The Salvage of Graft Occlusion in a Maintenace Hemodialysis Patient with Tuberous Sclerosis by Percutaneous Transluminal Angioplasty using Intravascular Ultrasound : Case Report.2004

    • Author(s)
      Higuchi T, Abe M, Okada K, Nakajima Y, Ohnishi Y, Hagi C, Fukuda N et al.
    • Journal Title

      Therapeutic Apheresis 8

      Pages: 164-167

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Complement 3 Is involved in the synthetic phenotype and exaggerated growth of vascular smooth muscle cells from spontaneously hypertensive rats.2004

    • Author(s)
      Lin Z-H, Fukuda N, et al.
    • Journal Title

      Hypertension 44

      Pages: 1-6

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Adenovirus-encoded hammerhead ribozyme to PDGF A-chain mRNA inhibits neointima formation after arterial injury.2004

    • Author(s)
      Lin Z-H, Fukuda N, et al.
    • Journal Title

      Journal of Vascular Research 41

      Pages: 305-313

    • Related Report
      2004 Annual Research Report
  • [Journal Article] A comparison of bicarbonate hemodialysis hemodiafiltration, and acetate-free biofiltration on cytokine production.2004

    • Author(s)
      Nakamura T, Fukuda N et al.
    • Journal Title

      Nihon University Journal of Medicine 63

      Pages: 360-366

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Chimeric DNA-RNA hammerhead ribozyme targeting TGF-β1 mRNA inhibits neointima formation in rat carotid artery after balloon injury.2004

    • Author(s)
      Higuchi T, Yamamoto C, Kuno T, Okada K, Soma M, Fukuda N, et al.
    • Journal Title

      Therapeutic Apheresis 8

      Pages: 460-467

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Chimeric DNA-RNA hammerhead ribozyme targeting to PDGF A- chain mRNA specifically inhibited neointimal formation of rat carotid artery after balloon injury2003

    • Author(s)
      Kotani M, Fukuda N, et al.
    • Journal Title

      Cardiovascular Research 57

      Pages: 265-276

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effects of antisense PNA to PDGF A-chain on growth of vascular smooth muscle cells2003

    • Author(s)
      Fukuda N, et al.
    • Journal Title

      Journal of Cardiovascular Pharmacol 42

      Pages: 224-231

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Sequence specificity, reactivity, and antitumor activity of DNA-alkylating pyrrole-imidazole diamides2003

    • Author(s)
      Bando T, Iida H, Tao ZF, Narita A, Fukuda N, et al.
    • Journal Title

      Chemical Biology 10

      Pages: 751-758

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Fmoc solid-phase synthesis and its application to pyrrole-imidazole polyamides2003

    • Author(s)
      Ayame H, Saito T, Bando T, Fukuda N
    • Journal Title

      Nucleic Acids Research 3

      Pages: 67-68

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Chimeric DNA-RNA hammerhead ribozyme targeting to PDGF A-chain mRNA specifically inhibited neointimal formation of rat carotid artery after balloon injury2003

    • Author(s)
      Kotani M, Fukuda N, Ando H, Hu W-Y, Kunimoto S, Kanmatsuse K, Saito S.
    • Journal Title

      Cardiovasc Res 57

      Pages: 265-276

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Effects of antisense PNA to PDGF A-chain on growth of vascular smooth muscle cells.2003

    • Author(s)
      Fukuda N, Furuya R, Kishioka H, Suzuki R, Matsuda H, Tahira Y, Takagi H, Ikeda Y, Saito S, Matsumoto K, Kanmatsuse K.
    • Journal Title

      J Cardiovasc Pharmacol 42

      Pages: 224-231

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Sequence specificity, reactivity, and antitumor activity of DNA-alkylating pyrrole-imidazole diamides.2003

    • Author(s)
      Bando T, Iida H, Tao ZF, Narita A, Fukuda N, Yamori T, Sugiyama H.
    • Journal Title

      Chem Biol 10

      Pages: 751-758

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Fmoc solid-phase synthesis and its application to pyrrole-imidazole polyamides.2003

    • Author(s)
      Ayame H, Saito T, Bando T, Fukuda N, Sugiyama H.
    • Journal Title

      Nucleic Acids Res 3(Suppl.)

      Pages: 67-68

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] 進行性腎障害の核酸医薬による遺伝子治療の開発 腎と透析2005

    • Author(s)
      福田 昇
    • Publisher
      東京医学社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] 核酸医薬による心血管病および進行性腎障害の遺伝子治療.特集、RNA工学の医学への展開2004

    • Author(s)
      福田 昇
    • Publisher
      最新医学社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] Therapeutic application of ribozymes for cardiovascular disease. "Synthetic Nucleic Acids as Inhibitors of Gene Expression : Mechanisms, Applications and Therapeutic Implications"2004

    • Author(s)
      Fukuda N
    • Publisher
      CRC Press Inc.
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Book] Therapeutic application of ribozymes for cardiovascular disease. "Synthetic Nucleic Acids as Inhibitors of Gene Expression : Mechanisms, Applications and Therapeutic Implications"2004

    • Author(s)
      Fukuda N.
    • Total Pages
      17
    • Publisher
      CRC Press Inc.
    • Related Report
      2004 Annual Research Report
  • [Patent(Industrial Property Rights)] TGF-β活性抑制剤2004

    • Inventor(s)
      福田 昇, 岸岡 博文, 上野 高浩, 杉山 弘
    • Industrial Property Rights Holder
      日本大学
    • Industrial Property Number
      2003-312365
    • Filing Date
      2004-09-03
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Patent(Industrial Property Rights)] TGF-β活性抑制剤2004

    • Inventor(s)
      福田 昇, 岸岡博文, 上野高浩, 杉山 弘
    • Industrial Property Rights Holder
      日本大学
    • Filing Date
      2004-08-14
    • Related Report
      2004 Annual Research Report
  • [Publications] Kotani M, Fukuda N, et al.: "Chimeric DNA-RNA hammerhead ribozyme targeting to PDGF A-chain mRNA specifically inhibited neointimal formation of rat carotid artery after balloon"Cardiovascular Research. 57. 265-276 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hu WY, Fukuda N, et al.: "Homogenous cultures of human-derived vascular smooth muscle cells produce angiotensin II by changing to the synthetic phenotype."Journal of Cell Physiology. 196. 284-292 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fukuda N, Furuya R et al.: "Effects of antisense PNA to PDGF A-chain on growth of vascular smooth muscle cells."Journal of Cardiovascular Pharmacology. 42. 224-231 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Bando T, Iida H, Tao ZF, Narita A, Fukuda N, et al.: "Sequence specificity, reactivity, and antitumor activity of DNA-alkylating pyrrole-imidazole diamides."Chemical Biology. 10. 751-758 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ando H, Fukuda N, et al.: "Chimeric DNA-RNA hammerhead ribozyme targeting TGF-β1 mRNA inhibits neointima formation in rat carotid artery after balloon injur"European Journal of Pharmacology. 483. 207-214 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ikeda Y, Fukuda N, et al.: "Development of angiogenic cell and gene therapy by transplantation of umbilical cord blood with vascular endothelial growth factor gene."Hypertension Research. 27. 119-128 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] 横山真一郎, 福田 昇: "血管の発生と新生-基礎と臨床-"メディカルレビュー社. 12 (2003)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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