2006 Fiscal Year Final Research Report Summary
Design and delivery of nucleic acid drugs for optimization of DNA vaccination
| Project/Area Number |
17390041
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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 |
Medical pharmacy
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| Research Institution | Kyoto University |
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Principal Investigator |
TAKAKURA Yoshinobu Kyoto Univ., Grad.Sch.Pharm.Sci, Professor, 薬学研究科, 教授 (30171432)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIKAWA Makiya Kyoto Univ., Grad.Sch.Pharm.Sci., Associate Professor, 薬学研究科, 助教授 (40273437)
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| Project Period (FY) |
2005 – 2006
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| Keywords | DNA vaccination / Dendritic cell / Plasmid DNA / Delivery / Cytotoxic T cell / Intracellular trafficking / CpG motif / Hsp70 |
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| Research Abstract |
DNA vaccination, which can induce humoral immunity as well as cellular immunity, is a promising approach for treatment of various infectious diseases and tumors. However, its optimization in terms of design and delivery is required to improve the efficacy of this strategy. In the present study, we examined cellular activation of dendritic cells, the most important cells affecting the efficacy of DNA vaccination, by plasmid DNA in naked and liposomal complex form. We found that dendritic cell activation takes place depending on CpG motifs contained in DNA in both naked and complex forms, which was quite contrast to the observation in macrophages in our previous studies. We also designed novel plasmid constructs encoding antigenic peptide-heat shock protein 70 fusion proteins for controlled intracellular trafficking and subsequent improved activity in cytotoxic T cell activation. We found that intradermal injection of the constructs in combination with electroporation could effectively induce antigen specific cytotoxic T cells and antitumor effect in mice. These findings would provide the useful basis for optimization of delivery and design of plasmid DNA for DNA vaccination.
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