1996 Fiscal Year Final Research Report Summary
Development of organ specific transfection methods by using liposomes.
| 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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| Keywords | liposomes / transfection / gene therapy / experimental nephritis / eye / eye drops / retina |
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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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[Publications] Zhao, D., Watarai, S., Lee, J., Kouchi, S., Ohmori, H.and Yasuda, T.: "Gene transfection by means of cationic liposomes : Comparison of the transfection efficiency of the liposomes prepared from the various positively charged lipids." Acta Medica Okayama. (in press).
Description
「研究成果報告書概要(欧文)」より
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[Publications] Lee, J., Tana, Watarai, S., Kakidani, H., Onuma, M., Zhao, D.and Yasuda, T.: "Evaluation of Cationic Liposomes for Delivery of Diphtheria Toxin A-Chain Gene to Cells Infected with Bovine Leukemia Virus." Japan Journal of Veterinary Medical Science. (in press).
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kashihara, N., Maeshima, Y., Morita, Y., Sugiyama, I., Sekikawa, T., Okamoto, K., Kanao, K., Yamasaki, Y., Makino, H., Ota, Z., and Yasuda, T.: "Inhibition of mesangial cell proliferation by antisense oligonucleotides targeting prooncgene mRNA." Japanese Journal of Inflammation. 15. 383-388 (1995)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kashihara, N., Maeshima, Y., Sugiyama, I., Sekikawa, T., Okamoto, K., Morita, Y., Kanao, K., Yamasaki, Y., Makino, H., Ota, Z., Yasuda, T., and Nakanishi, M.: "Inhibition of mesangial cell proliferation and matrix expansion by antisense oligonucleotides." Recent Avances in Molecular Nephrology. KOHKO-DO,Niigata, Japan. 1-11 (1995)
Description
「研究成果報告書概要(欧文)」より
