2004 Fiscal Year Final Research Report Summary
Development of gene therapy for progressive renal diseases by ribozyme
| Project/Area Number |
15590863
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Nihon University |
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Principal Investigator |
FUKUDA Noboru Nihon University, School of Medicine, Instructor, 医学部, 講師 (40267050)
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| Co-Investigator(Kenkyū-buntansha) |
MATSUMOTO Koichi Nihon University, School of Medicine, Professor, 医学部, 教授 (00125064)
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| Project Period (FY) |
2003 – 2004
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| Keywords | PDGF A-chain / TGF-b1 / ribozyme / adeno virus / kidney disease |
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| 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.
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[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.
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Journal Title
J Pharmacol Exp Therap (submitting)
Description
「研究成果報告書概要(欧文)」より
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[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.
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Journal Title
Hypertension (submitting)
Description
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[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.
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Journal Title
J Cardiovasc Pharmacol 42
Pages: 224-231
Description
「研究成果報告書概要(欧文)」より
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