1998 Fiscal Year Final Research Report Summary
PREPARATION OF FUSOGENIC LIPOSOMES USING FUSOGENIC POLYPEPTIDES AND THEIR APPLICATION TO GENE DELIVERY SYSTEMS
| Project/Area Number |
09680858
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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 |
Biomedical engineering/Biological material science
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| Research Institution | OSAKA PREFECTURE UNIVERSITY |
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Principal Investigator |
TAKAGISHI Toru OSAKA PREFECTURE UNIVERSITY,DEPARTMENT OF APPLIED MATERIALS SCIENCE,PROFESSOR, 工学部, 教授 (50081336)
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| Co-Investigator(Kenkyū-buntansha) |
MORIMOTO Keiji OSAKA PREFECTURE UNIVERSITY,DEPARTMENT OF APPLIED MATERIALS SCIENCE,RESEARCH ASS, 工学部, 助手 (20239693)
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| Project Period (FY) |
1997 – 1998
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| Keywords | LIPOSOME / GENE THERAPY / MEMBRANE FUSION / AMPHIPHILIC POLYMER / POLYPEPTIDE / THERMOSENSITIVE POLYMER / DRUG DELIVERY SYSTEMS / GENE DELIVERY |
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| Research Abstract |
Liposomes with fusogenic activity were developed using amphiphilic polypeptides and synthetic polymers. It was found that liposomes bearing an amphiphilic polypeptide having glutamic acid residues revealed enhanced fusogenic ability under an acidic condition. Liposomes modified with poly(glycidol) having beta-alanine residues exhibited fusogenic activity to negatively charged membranes. Gene delivery into cos-l cells was examined using the liposomes modified with poly(glycidol) with beta-alanine residues. The cells treated with the polymer-modified liposomes encapsulating plasmid DNA containing chloramphenicol transferase gene exhibited the enzymatic activity, indicating that the liposomes could deliver the plasmid DNA into the cells. Also, complexes of cationic lipid, plasmid DNA, and liposomes modified with succinylated po1xy(glycidol) were prepared and transfection of cancer cells mediated by these complexes was studied. The cells treated with the complexes did not reveal the enzymatic activity. However, the cells treated with the complexes bearing transferrin exhibited strong enzymatic activity. It is likely that the complexes introduced the plasmid DNA by binding the cells via transferrin-transferrin receptor interaction. Thus, the complexes may be useful as a gene delivery system with target-specificity In addition, liposomes modified with thermosensitive polymers were prepared. It was found that contents release and/or fusogenic activity of these liposomes could be controlled by ambient temperature. These Liposomes might have potential usefulness as a carrier of biologically active molecules site specificity.
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