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In vivo evaluation of plasmid DNA encoding OP-1 protein for spine fusion.

Bright C, Park YS, Sieber AN, Kostuik JP, Leong KW

Department of Biomedical Engineering, School of Medicine, Johns Hopkins University, Baltimore, MD, USA.

STUDY DESIGN: A posterolateral lumbar interbody arthrodesis animal model was selected to evaluate the percutaneous delivery of OP-1 plasmid DNA. OBJECTIVE.: To evaluate the feasibility of achieving ectopic bone formation using nonviral gene delivery with a minimally invasive technique, by coinjecting plasmid DNA encoding OP-1 with collagen into the paraspinal muscle. SUMMARY OF BACKGROUND DATA: Osteoinductive proteins show great promise for achieving spine fusion but suffer from poor bioavailability. Viral gene transfer can produce therapeutic and sustained levels of osteoinductive proteins to achieve osteogenesis in a variety of animal models. Toxicity and immunogenicity concerns, however, limit the appeal of viral gene therapy for spine fusion. METHODS: Single-level posterior lumbar arthrodesis was attempted at L5-L6 in 64 adult Sprague-Dawley rats bilaterally. OP-1 plasmid DNA was injected with and without collagen carrier above the L5 transverse process either percutaneously or after open surgery. Bone formation was evaluated at 2 and 4 weeks by manual palpation, posterolateral radiographs, and nondecalcified histology. Control animals received the rhOP-1 protein. RESULTS: Bone formation was detected histologically after the percutaneous and open surgical delivery of 25 microg or 500 microg, respectively, of OP-1 plasmid DNA (pVR1055-OP1) and collagen (bone formation = 75% and 50%), but was weaker than that observed after injection of 30 microg of rhOP-1 protein and collagen (bone formation = 100%). Single-level spine fusion was only achieved in groups receiving percutaneous OP-1 protein and collagen (30 microg protein, fusion rate = 100%) or high concentrations of OP-1 protein alone (40 microg protein, 100%), as confirmed through manual palpation, histology, and radiography. CONCLUSIONS.: These data confirm that OP-1 plasmid DNA can successfully generate bone formation in vivo.

Published 1 September 2006 in Spine, 31(19): 2163-72.
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