{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T15:41:17Z","timestamp":1760888477301},"reference-count":32,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2010,11,9]],"date-time":"2010-11-09T00:00:00Z","timestamp":1289260800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2010,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Bone morphogenetic protein\u20102 (BMP\u20102) is an osteoinductive protein and is considered useful for the treatment of skeletal disorders. Previous studies using BMP\u20102 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\u20102. Although viral vector\u2010mediated gene transfer is efficient, safety concerns prevent its clinical application for common diseases. On the other hand, plasmid\u2010based gene transfer is a safe method and can be harnessed for practical applications.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A plasmid encoding human BMP\u20102 (pCAGGS\u2010BMP\u20102) 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\u20102 production was assessed via immunohistochemistry, and osteoinduction was evaluated using radiography, histology and biochemical assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The BMP\u20102 gene was transferred into the skeletal muscle of mice by repeat injection using pCAGGS\u2010BMP\u20102. Mature bone was frequently observed in mice injected repeatedly with pCAGGS\u2010BMP\u20102 at a divided dose. This confirms that, if the total dose is fixed, repeat injection with pCAGGS\u2010BMP\u20102 at a divided dose causes osteoinduction more frequently in the skeletal muscle of mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results suggest the possibility of the effective clinical use of human BMP\u20102 gene therapy by direct DNA injection, and facilitate the clinical application of BMP\u20102 gene therapy. 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