TY - JOUR
T1 - Gene therapy for the regeneration of bone
AU - Evans, Christopher
N1 - Funding Information:
The author's work in this area has been supported by The Orthopaedic Trauma Association , NIH grant R01 AR 050243 from NIAMS and the AO Foundation.
PY - 2011/6
Y1 - 2011/6
N2 - 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.
AB - 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.
KW - Adeno-associated virus
KW - Adenovirus
KW - Allograft revitalization
KW - Animal model
KW - Clinical trial
KW - Gene activated matrix
KW - Osteoblast
KW - Osteoprogenitor cell
KW - Vector
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U2 - 10.1016/j.injury.2011.03.032
DO - 10.1016/j.injury.2011.03.032
M3 - Article
C2 - 21489526
AN - SCOPUS:79957797244
SN - 0020-1383
VL - 42
SP - 599
EP - 604
JO - Injury
JF - Injury
IS - 6
ER -