2003 Fiscal Year Final Research Report Summary
Development of novel synthetic gene delivery systems with an ability to fuse with cells
| Project/Area Number |
13558115
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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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 |
KONO Kenji Osaka Prefecture University, Dept.of Applied Materials Science, Professor, 工学研究科, 教授 (90215187)
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| Co-Investigator(Kenkyū-buntansha) |
MARUYAMA Kazuo Teikyo University, Department of Pharmaceutics, Professor, 薬学部, 教授 (30130040)
MORIMOTO Keiji Osaka Prefecture University, Department of Applied Materials Science, Research Associate, 工学研究科, 助手 (20239693)
TAKAGISHI Toru Osaka Prefecture University, Department of Applied Materials Science, Professor, 工学研究科, 教授 (50081336)
YASUKOCHI Toru NOF Co.,OLEO Chemicals, Research Laboratory, Group Leader, 油化学研究所, グループリーダー(研究職)
YANAGIE Hironobu The university of Tokyo, Research Center for Advanced Science and Technology, Associate Professor, 先端科学技術研究センター, 助教授 (30212278)
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| Project Period (FY) |
2001 – 2003
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| Keywords | gene therapy / non-viral vector / gene delivery / nano-bio / lipoplex / liposome / dendrimer / biomaterial |
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| Research Abstract |
In this study, we attempted to develop novel gene delivery systems that transfect cells efficiently by fusing with cells. We have previously found that succinylated oly(glycidol) exhibits fusogenic activity under weakly acidic conditions. Thus, to improve its fusogenic activity, hydrophobic groups were introduced. While the introduction of hydrophobic did not enhance its fusogenic activity, the polymer with higher succinylated unit content showed stronger activity to promote membrane fusion. We prepared liposomes modified with the succinylated poly(glycidol) with the optimized structure. The polymer-modified liposomes exhibited strong fusion ability. We next prepared complexes formed between the fusogenic liposomes and lipoplexes (cationic lipid-DNA complexes) or polyplexes (cationic polymer-DNA complexes) as new types of gene delivery systems with fusogenic activity. We found that the fusogenic liposome-lipoplex complexes achieved more efficient transfection of various cells than conventional non-viral vectors, such as DC-chol. In addition, these complexes were less toxic to cells than these conventional vectors. We also developed a new synthetic vector, dendrimer lipids, which exhibited an efficient transfection through a synergy of membrane fusion and the proton sponge effect. It is concluded that membrane fusion is an efficient strategy to achieve an efficient transfection of cells.
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