2007 Fiscal Year Final Research Report Summary
Development of multi-functional nanocarrier of siDNA and application for bone and joint diseases
| Project/Area Number |
17390412
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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 |
Orthopaedic surgery
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| Research Institution | The University of Tokyo |
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Principal Investigator |
ITAKA Keiji The University of Tokyo, Graduate School of medicine, Lecturer (60292926)
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| Co-Investigator(Kenkyū-buntansha) |
CHUNG Ung-il The University of Tokyo, Graduate School of Engineering, Professor (30345053)
KAWAGUCHI Hiroshi The University of Tokyo, Hospital, Associate Professor (40282660)
NAKAMURA Kozo The University of Tokyo, Hospital, Professor (60126133)
KATAOKA Kazunori The University of Tokyo, Graduate School of Engineering, Professor (00130245)
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| Project Period (FY) |
2005 – 2007
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| Keywords | siRNA / delivery system / nanocarrier / bone and joint disease / nanotechnology / polyplex micelle |
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| Research Abstract |
In this project, we developed the nanocarriers containing siRNA and analyzed the biological functions.
1. Molucular design of nanocarriers The nanocarriers were composed of siRNA (or siRNA conjugate) and cationic polymers. The formation of nanocarriers with narrow distribution was confirmed.
2. Growth inhibition of cultured cells on the spheroid culture system After applying RecQL1 siRNA using this nanocarrier, the growth of spheroid-shaped cells was effectively inhibited after a week of application. This effect was observed in a low concentration, indicating the stability of nanocarriers in the physiological condition, smooth penetration inside the spheroids, and facilitated uptake by the receptor-targeting ligands.
3. Evaluation of biocompatibility By the evaluation of cytotoxicity and biocompatibility using cultured cells, this nanocarrier was revealed to have minimal cytotoxicity. In addition, the expressions of house-keeping genes were not affected by the nanocarrier, indicating the excellent biocompatibility.
4. In vivo bone regeneration This nanocarrier was revealed to have good capacity for inducing cell differentiation, due to the high transfection efficiency, excellent biocompatibility and a sustained manner of gene expression. By applying this nanocarrier to the bone-defect model of mice, the better bone regeneration was induced compared to that by the adenoviral vector. We are planning to apply the siRNA nanocarriers to the in vivo studies with modifications such as installation of disulfide bonds into the carriers.
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