The adeno associated viral vector as a strategy for intradiscal gene transfer in immune competent and pre-exposed rabbits

Christian Lattermann, William M. Oxner, Xiao Xiao, Juan Li, Lars G. Gilbertson, Paul D. Robbins, James D. Kang

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Study Design. Experimental animal study. Objectives. This study evaluates the in vitro and in vivo transduction efficacy and transgene expression in immune competent and pre-exposed rabbits Summary of Background Data. Degenerative disc disease (DDD) continues to pose a substantial clinical problem. Therapeutic options such as an interbody fusion are highly invasive and result in the loss of the intervertebral disc. In addition, interbody fusion puts the adjacent discs at an even higher risk for disc degeneration. A novel approach to slow DDD is to introduce high levels of growth factors into the degenerating disc by delivering the gene coding for the appropriate growth factor. The most efficient technique to do so to date uses viral vectors. However, viral vectors may be problematic because of their immunogenicity. The adeno-associated virus (AAV) viral vector is known to be less immunogenic than commonly used adenoviral vectors. Methods. Human nucleus pulposus cells were transduced in vitro. Twenty-four Rabbits were injected with AAV viral vectors carrying different marker genes. Transgene expression and the humoral/cellular immune response to the vector was evaluated. Results. We could show that the AAV viral vector transduces human as well as rabbit nucleus pulposus cells in vitro and in vivo. There is a significant humoral immune response against the AAV vector that decreases transgene expression over 10-fold in preimmunized animals. Conclusions. AAV is a valuable new vector to achieve transgene expression in the intervertebral disc. In preimmunized animals, its use needs to be further evaluated because of the significant reduction in transgene expression.

Original languageEnglish (US)
Pages (from-to)497-504
Number of pages8
JournalSpine
Volume30
Issue number5
DOIs
StatePublished - Mar 1 2005
Externally publishedYes

Keywords

  • Disc
  • Gene therapy
  • Nucleus
  • Spine
  • Viral vector

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