Simple strategy for bone regeneration with a BMP-2/7 gene expression cassette vector

Bone morphogenetic protein (BMP) is one of the most promising candidates for bone regeneration therapy. Heterodimers of BMP family proteins, such as BMP-2/4 or BMP-2/7, are well known to have stronger osteoinduction activity than BMP homodimers. Here, we constructed a double gene cassette vector encoding BMP-2 and BMP-7, pCAGGS-BMP-2/7, and examined its potential for osteoinduction in vitro and in vivo. Expression of the pCAGGS-BMP-2/7 vector induced osteogenic differentiation in various cell lines with the same efficiency as BMP-2 and BMP-7 co-expressed from separate vectors. Moreover, the pCAGGS-BMP-2/7 vector strongly induced bone formation in rat skeletal muscle when introduced by in vivo electroporation, compared with BMP-2 or BMP-7 alone. Thus, our BMP-2/7 double gene cassette vector, or some variation of it, may be applicable for the future clinical induction of bone formation, because it does not require multiple vectors or complicated preparation.