Gene therapy for the regeneration of bone.

Gene transfer technologies offer the prospect of enhancing bone regeneration by delivering osteogenic gene products locally to osseous defects. In most cases the gene product will be a protein, which will be synthesized endogenously within and around the lesion in a sustained fashion. It will have undergone authentic post-translational processing and lack the alterations that occur when recombinant proteins are synthesized in bioreactors and stored. Several different ex vivo and in vivo gene delivery strategies have been developed for this purpose, using viral and non-viral vectors. Proof of principle has been established in small animal models using a variety of different transgenes, including those encoding morphogens, growth factors, angiogenic factors, and transcription factors. A small number of studies demonstrate efficacy in large animal models. Developing these promising findings into clinical trials will be a long process, constrained by economic, regulatory and practical considerations. Nevertheless, the overall climate for gene therapy is improving, permitting optimism that applications in bone regeneration will eventually become available.