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Gene therapy for bone healing

Published online by Cambridge University Press:  23 June 2010

Christopher H. Evans
Christopher H. Evans
Affiliation:
Center for Advanced Orthopaedic Studies, Beth-Israel Deaconess Medical Center, Harvard Medical School, 330, Brookline Avenue, RN-115, Boston, MA 02215, USA and Collaborative Research Center, AO Foundation. E-mail: [email protected]
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Abstract

Clinical problems in bone healing include large segmental defects, spinal fusions, and the nonunion and delayed union of fractures. Gene-transfer technologies have the potential to aid healing by permitting the local delivery and sustained expression of osteogenic gene products within osseous lesions. Key questions for such an approach include the choice of transgene, vector and gene-transfer strategy. Most experimental data have been obtained using cDNAs encoding osteogenic growth factors such as bone morphogenetic protein-2 (BMP-2), BMP-4 and BMP-7, in conjunction with both nonviral and viral vectors using in vivo and ex vivo delivery strategies. Proof of principle has been convincingly demonstrated in small-animal models. Relatively few studies have used large animals, but the results so far are encouraging. Once a reliable method has been developed, it will be necessary to perform detailed pharmacological and toxicological studies, as well as satisfy other demands of the regulatory bodies, before human clinical trials can be initiated. Such studies are very expensive and often protracted. Thus, progress in developing a clinically useful gene therapy for bone healing is determined not only by scientific considerations, but also by financial constraints and the ambient regulatory environment.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 12 , January 2010 , e18
Copyright
Copyright © Cambridge University Press 2010

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References

References

The following website compiles information on human gene therapy clinical trials:

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