Table 1.

In Vivo Gene Therapy for Bone Regeneration

Vector and Gene	Target Site	Main Results	Reference
Adenoviral BMP-7	Ectopic site (subcutaneous and intramuscular) in a mouse model	Induced bone formation 4 weeks following implantation	Franceschi et al., 2000 [45]
Adenoviral BMP-2	Ectopic site (intramuscular) in a mouse model	Bone was formed 2 weeks following gene delivery in immunodeficient mice and 3 weeks following gene delivery in immunocompetent mice	Musgrave et al., 1999 [42]
Adenoviral BMP-9	Injection into thigh muscles of athymic rats or Sprague-Dawley rats	Bone volume obtained in athymic rats was 3 times higher than that noted in immunocompetent animals	Li et al., 2003 [41]
Adenoviral BMP-2	Rabbit femur segmental defect model	After 7 weeks, robust bone formation was noted in the defect sites and some defects were bridged by new bone	Baltzer et al., 2000 [48]
Adenoviral BMP-2	Femur segmental defect regeneration in a rat model	50% of defects were bridged with mature bone that did not contain cartilage islands 8 weeks after gene delivery	Betz et al., 2006 [49]
Adenoviral BMP-2	Femur segmental defect regeneration in a rat model	When the adBMP-2 injection was delayed until 10 days after defect formation, 86% of defects were bridged with bone, compared with no defects when gene delivery occurred during defect formation and 50% of defects when the adenovector was injected 1 day later	Betz et al., 2007 [50]
Adenoviral BMP-2	High dose of adBMP-2 injected 5 days after defect formation in a rat femur segmental defect model	100% bridging of defects 8 weeks following gene delivery	Betz et al., 2007 [47]
Adenoviral BMP-2 or BMP-6	Osteochondral defects in a femoral condyle in a pony model	Bone formation failed to provide long-term healing	Menendez et al., 2011 [52]
Adenoviral BMP-2	Tibia bone defects in an osteoporotic sheep model	Induced faster defect healing, higher callus stiffness during the initial stages of the healing process	Egermann et al., 2006 [53]
AAV rhBMP-2 under TetON regulation	Ectopic site (intramuscular) and critically sized calvarial defects in a mouse model	Mice that were given Dox demonstrated bone formation in both in vivo models compared to none in mice prevented from receiving Dox	Gafni et al., 2004 [56]
rAAV-caAlk2	Mouse femoral allograft Model	Complete bridging of bone around a cortical allograft was possible	Koefoed et al., 2005 [58]
scAAV2.5-BMP2	Mouse femoral allograft model	scAAV2.5-BMP2 allografts formed a new cortical shell that was indistinguishable from that formed by live autografts	Yazici et al., 2011 [59]
Retroviral fused BMP-2/4	Femoral fracture in a rat model	Healing was achieved in a similar rate to untreated controls and was followed by production of massive amounts of ectopic bone that eventually remodeled	Rundle et al., 2003 [44]
Retroviral COX-2	Femoral fracture in a rat model	Faster healing (3 vs. 5 weeks in the control group) and avoided ectopic bone formation	Rundle et al., 2008 [63]
naked DNA, BMP-2	Repeated injections (1 –8 times) into the skeletal muscle of mice at a divided dose	Bone formation was more frequent when more injections were used	Osawa et al., 2010 [40]
GAM, BMP-4	Femoral osteotomy model in rats	Bridging of the gap observed after 9 weeks, while healing was achieved after 18 weeks	Fang et al., 1996 [39]
GAM, BMP-4 & PTH1–34		Bridging was observed at 4 weeks and healing at 12 weeks
GAM, PTH1–34	Canine tibia osteotomy model	Connection found between bone formation and both the dose of plasmid DNA delivered and defect size	Bonadio et al., 1999 [64]
Sonoporation, BMP-9	Ectopic (intramuscular) bone formation in a mouse model	Gene activity was limited for several weeks and no tissue damage was found	Sheyn et al., 2008 [30]
Electroporation, BMP-9	Nonunion radial defect regeneration in a mouse model	Complete healing of the bone defect 5 weeks following gene delivery	Kimelman-Bleich et al., 2011 [35]
Liposome-mediated BMP-2	Peri-implant bone defects in a porcine calvaria model	New bone formation was enhanced compared with control groups	Park et al., 2006 [69]