| Project/Area Number |
07670174
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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 |
Pathological medical chemistry
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| Research Institution | Okayama University |
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Principal Investigator |
YASUDA Tatsuji Okayama University Medical School, Professor, 医学部, 教授 (30092357)
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| Co-Investigator(Kenkyū-buntansha) |
WATARAI Shinobu Okayama University Medical School, Lecturer, 医学部, 講師 (50175139)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1996: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1995: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | liposomes / transfection / gene therapy / experimental nephritis / eye / eye drops / retina / 陽性荷電リポソーム / トランスフェクション / ルシフェラーゼ遺伝子 / 眼球 / 腎炎モデル / 転写因子 E2F / decoy DNA |
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| Research Abstract |
We compared the transfection efficiency of the positively charged liposomes composed of various lipids. In the cationic liposomes used, the liposomes composed of TMAG,DOPE,and DLPC showed an much higher efficiency for the plasmid DNA entrapment, and gave highly efficient transfection in the absence or presence of serum. The transfection efficiency of the cationic liposomes is affected by the lipid composition, type of liposomes, or the presence of serum.
We investigated whether cationic liposomes are efficient at delivering the gene fo diphtheria toxin A-chain (DT-A) under the control of the long terminal repeats of lovine leukemia virus (BLV) in to BLV-infected cells and are also sutable for in vivo use. The cationic liposomes may be efficient transfection reagent for the BLV-infected cells and can be utilized for DT-A gene delivery into BLF-infected cells in vivo.
Efficient and stable transfer of the functional gene could be achived by injection of liposomes in the cornea, iris, ciliary body, and retina of rats. We showed that instillation as eye drops of an expression plasmid vector carried by the specific kinds of liposomes could transfer the gene to the reinal ganglion cells of rat, without causing any inflammation. This non-surgical, convenient way for gene delivery to the reina would facilitate the development of treatment for vsrious inraocular desease.
Anti-proliferative effect of antisense oliponucleotides targeting the proto-oncogenes and cell-cycle associated nuclear proteins on mesangial cells by tranfection of liposome methods were examined. The antisense oligonucleotides suppressed the mesagial cell proliferation. Antisense TGF-beta and PDGF-B chain inhibited accumulation of extracellular matrix and mesangial cell proliferation in Thy 1 glomelonephritis model. These results indicate the feasibility of antisense oligonucleotide as a novel class of therapeutic agents in the treatment of glomerular diseases.
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