Int J Med Sci 2006; 3(3):97-105. doi:10.7150/ijms.3.97
Comparison of osteogenic potentials of human rat BMP4 and BMP6 gene therapy using [E1-] and [E1-,E2b-] adenoviral vectors
1 Departments of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia 22908, USA
2 Genetics Institute, Andover, Massachusetts 01810, USA
3 Departments of Pediatrics and Human Genetics, Duke University Medical Center, Durham, North Carolina 27710, USA
4 Departments of Biomedical Engineering, University of Virginia Health System, Charlottesville, Virginia 22908, USA
Li H, Li JZ, D. Pittman D, Amalfitano A, Hankins GR, Helm GA. Comparison of osteogenic potentials of human rat BMP4 and BMP6 gene therapy using [E1-] and [E1-,E2b-] adenoviral vectors. Int J Med Sci 2006; 3(3):97-105. doi:10.7150/ijms.3.97. Available from http://www.medsci.org/v03p0097.htm
Osteogenic potentials of some recombinant human bone morphogenetic protein (BMP) first-generation adenoviral vectors (ADhBMPs) are significantly limited in immunocompetent animals. It is unclear what role expression of viral proteins and foreign proteins transduced by adenoviral vectors play in the host immune response and in ectopic bone formation. In this study two sets of experiments were designed and performed. First, rat BMP6 cDNA were amplified, sequenced, and recombined in first-generation adenoviral vector (ADrBMP6). A comparison of human and rat BMP6 adenoviral vectors demonstrated identical osteogenic activities in both immunodeficient and immunocompetent rats. Second, the activities of recombinant human BMP6 in E1- (ADhBMP6) and [E1-,E2b-] ( [E1-,E2b-]ADGFP&hBMP6, and [E1-,E2b-]ADhBMP6) adenoviral vectors were compared in both in vitro and in vivo models. Similar activities of these two generations of BMP adenoviral vectors were found in all models. These results indicate that the amount of viral gene expression and the source of the BMP cDNA are not major factors in the interruption of osteogenic potentials of recombinant BMP6 adenoviral vectors in immunocompetent animals.