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

Corinne Bright, Ye Soo Park, Ann N. Sieber, John P. Kostuik, Kam W. Leong

Research output: Contribution to journalArticle

Abstract

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 μg or 500 μg, 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 μg 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 μg protein, fusion rate = 100%) or high concentrations of OP-1 protein alone (40 μg 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.

Original languageEnglish (US)
Pages (from-to)2163-2172
Number of pages10
JournalSpine
Volume31
Issue number19
DOIs
StatePublished - Sep 1 2006

Keywords

  • Bone morphogenetic protein
  • Graft substitute
  • Lumbar spine fusion
  • Nonviral
  • Osteogenic protein-1
  • Plasmid DNA
  • Skeletal muscle

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Clinical Neurology

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  • Cite this

    Bright, C., Park, Y. S., Sieber, A. N., Kostuik, J. P., & Leong, K. W. (2006). In vivo evaluation of plasmid DNA encoding OP-1 protein for spine fusion. Spine, 31(19), 2163-2172. https://doi.org/10.1097/01.brs.0000232721.59901.45