2006 Fiscal Year Final Research Report Summary
Preparation of efficient gene vectors with multi functions
| Project/Area Number |
16300159
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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 | 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 |
KONO Kenji Osaka Prefecture University, Graduate School of Engineering, Professor, 工学研究科, 教授 (90215187)
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| Co-Investigator(Kenkyū-buntansha) |
HARADA Atsush Osaka Prefecture University, Graduate School of Engineering, Associate Professor, 工学研究科, 助教授 (50302774)
EMI Nobuhiko Fujita Health University, School of Medicine, Associate Professor, 医学部, 助教授 (30185144)
KADOWAKI Norimitsu Kyoto University, School of Medicine, Lecturer, 医学研究科, 講師 (60324620)
KOJIMA Chie Osaka Prefecture University, Graduate School of Engineering, Instructor, 工学研究科, 助手 (50405346)
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| Project Period (FY) |
2004 – 2006
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| Keywords | gene therapy / non-viral vector / gene delivery / nano-bio / lipoplex / liposome / drug delivery system / nano-medicine |
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| Research Abstract |
In this study, we attempted to develop highly efficient nonviral vectors with multi-functions according to two different approaches, namely liposome-based systems with fusogenic polymers and dendrimer-based systems. First, we prepared complexes of lipoplexes and liposomes modified with pH-sensitive fusogenic polymer, succinylated poly(glycidol) with transferrin, which is a cancer cell-specific ligand. We found that the complexation of the fusogenic polymer-modified liposomes enhanced ability of the lipoplexes as gene vectors. We also examined the influence of the complex size on its transfection activity and found that decrease in the size resulted in increase in transfection activity. The obtained complexes with small size exhibited high transfection activity in the presence of serum proteins, which often decreases transfection activity of gene vectors. We further attempted to improve transfection activity of the lipoplexes-fusogenic liposomes complexes by increasing fusogenic ability
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of the liposomes. For this purpose, we synthesized several fusogenic polymers with hydrophobic side groups. We found that fusogenic activity of the polymers increased with increasing hydrophobicity of the polymers. In addition, transfection activity of the complexes of the lipoplexes and polymer-modified liposomes exhibited extremely high transfection activity when the polymer with the highest fusogenic activity was used for the liposome modification. It was noteworthy that the obtained complexes achieved efficient transfection of DC 2.4, which is derived from dendritic cell. On the other hand, we also attempted to develop a new type of synthetic vector by using dendritic molecules, which achieve efficient transfection through so-called proton sponge effect. We prepared a new family of cationic lipids, which consist of a polyamidoamine dendron moiety and two long alkyl groups. These molecules formed complexes with DNA. The obtained complexes achieved efficient transfection of cells through a synergetic action of the proton sponge effect and membrane fusion. In addition, we attached polyethylene glycol chains to all chain ends of the dendron moiety. The obtained polyethylene glycol-modified dendron-bearing lipids were found to be useful for preparation of vectors with colloidal stability and high transfection activity. We believe that information obtained through this study will contribute for establishment of safe and efficient gene therapy. Less
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