期刊
JOURNAL OF GENE MEDICINE
卷 12, 期 12, 页码 937-944出版社
JOHN WILEY & SONS LTD
DOI: 10.1002/jgm.1515
关键词
bone; bone morphogenetic protein; injection; nonviral gene transfer; osteoinduction; plasmid DNA
资金
- Japanese Ministry of Education, Science, Sports and Culture [21390533]
- Grants-in-Aid for Scientific Research [21390533] Funding Source: KAKEN
Background Bone morphogenetic protein-2 (BMP-2) is an osteoinductive protein and is considered useful for the treatment of skeletal disorders. Previous studies using BMP-2 in clinical applications have encountered difficulties, including the lack of an efficient, safe, inexpensive and simple delivery system. The gene transfer approach is a promising option for utilizing BMP-2. Although viral vector-mediated gene transfer is efficient, safety concerns prevent its clinical application for common diseases. On the other hand, plasmid-based gene transfer is a safe method and can be harnessed for practical applications. Methods A plasmid encoding human BMP-2 (pCAGGS-BMP-2) was used and injected repeatedly (one to eight times) into the skeletal muscle of mice at a divided dose. We compared the capability of osteoinduction in the skeletal muscle of mice after gene transfer by repeat injection. BMP-2 production was assessed via immunohistochemistry, and osteoinduction was evaluated using radiography, histology and biochemical assays. Results The BMP-2 gene was transferred into the skeletal muscle of mice by repeat injection using pCAGGS-BMP-2. Mature bone was frequently observed in mice injected repeatedly with pCAGGS-BMP-2 at a divided dose. This confirms that, if the total dose is fixed, repeat injection with pCAGGS-BMP-2 at a divided dose causes osteoinduction more frequently in the skeletal muscle of mice. Conclusions These results suggest the possibility of the effective clinical use of human BMP-2 gene therapy by direct DNA injection, and facilitate the clinical application of BMP-2 gene therapy. Copyright (c) 2010 John Wiley & Sons, Ltd.
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