2000 Fiscal Year Final Research Report Summary
DEVELOPMENT OF THE METHOD OF GENE DELIVERY USING BLOCK COPOLYMER FOR THE TREATMENT OF CARDIOVASCULAR DISEASES
| Project/Area Number |
11838022
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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 Institution | NATIONAL CARDIOVASCULAR CENTER RESEARCH INSTITUTE |
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Principal Investigator |
SEHIBA Mariko NATIONAL CARDIOVASCULAR CENTER RESEARCH INSTITUTE, DEPARTMENT OF CARDIOVASCULAR DYNAMICS STAFF SCIENTIST, 循環動態機能部, 室員 (70271575)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMOKADO Kentaro TOKYO MEDICAL AND DENTAL UNIVERSITY DEPARTMENT OF MEDICINE PROFESSOR, 大学院・医歯学総合研究科, 教授 (30192115)
KATAOKA Kasunori UNIVERSITY OF TOKYO DEPARTMENTS OF MATERIALS SCIENCE PROFESSOR, 大学院・工学系研究科, 教授 (00130245)
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| Project Period (FY) |
1999 – 2000
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| Keywords | GENE THERAPY / NON-VIRAL VECTOR / BLOCK COPOLYMER / PIC MICELLES / HEP G2 CELL / CATIONIC POLYMER / LIVER / POLY-L-LYSINE |
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| Research Abstract |
To establish non-viral gene delivery systems for intravenous administration, complexes of DNA and block copolymer consisting of poly-L-lysine and poly(ethylene glycol) were tested in in vivo turnover studies. The polyion complex micelles have self-assembling core-shell structures, yielding spherical particles with diameters of 30-40 nm as determined by electron microscopy. Southern blot analysis showed that supercoiled DNA was observed for 30 min and opencircular or linear DNA was seen for 3 hr after intravenous administration of PIC micelles having the charge ratios of 1 : 4 and PLL length of 48 mer. The PIC micelles with shorter PLL length showed lower stability in the blood stream. It was suggested that DNA is able to persist as an intact molecule in the blood stream using this system. Though having no ligands, PIC micelles with charge ratios of 1 : 2 and 1 : 4 transfected efficiently into HepG2 cells. Preincubation with free copolymer inhibited expression of the reporter gene, suggesting that adhesion of block copolymer to the cell surface blocked the interaction site of the PIC micelles. When the PIC micelles were injected via supramesenteric vein, expression of the gene was observed only in the liver. The expression of the luciferase gene was sustained for 3 days. It was suggested that this gene delivery system is intrinsically efficient.
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[Publications] Croniger CM,Millward C,Yang J,Kawai Y,Arinze IJ,Liu S,Harada-Shiba M,Chakravarty K,Friedman JE,Poli V,Hanson RW.: "Mice with a deletion in the gene for CCAAT/enhancer-binding protein beta have an attenuated response to cAMP and impaired carbohydrate metabolism"J Biol Chem.. 276. 629-638 (2001)
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「研究成果報告書概要(欧文)」より
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