TY - JOUR
T1 - Gene delivery to bone
AU - Evans, C. H.
N1 - Funding Information:
The author's work in this area has been funded by the Orthopaedic Trauma Association , NIH (NIAMS grant R01 AR050243 ) and the AO Foundation . I thank Prof. Hamish Simpson and Dr. Michael Kelly for permission to cite their unpublished data, and Prof. Topher Niyibizi for reading a draft of the manuscript.
PY - 2012/9
Y1 - 2012/9
N2 - Gene delivery to bone is useful both as an experimental tool and as a potential therapeutic strategy. Among its advantages over protein delivery are the potential for directed, sustained and regulated expression of authentically processed, nascent proteins. Although no clinical trials have been initiated, there is a substantial pre-clinical literature documenting the successful transfer of genes to bone, and their intraosseous expression. Recombinant vectors derived from adenovirus, retrovirus and lentivirus, as well as non-viral vectors, have been used for this purpose. Both ex vivo and in vivo strategies, including gene-activated matrices, have been explored. Ex vivo delivery has often employed mesenchymal stem cells (MSCs), partly because of their ability to differentiate into osteoblasts. MSCs also have the potential to home to bone after systemic administration, which could serve as a useful way to deliver transgenes in a disseminated fashion for the treatment of diseases affecting the whole skeleton, such as osteoporosis or osteogenesis imperfecta. Local delivery of osteogenic transgenes, particularly those encoding bone morphogenetic proteins, has shown great promise in a number of applications where it is necessary to regenerate bone. These include healing large segmental defects in long bones and the cranium, as well as spinal fusion and treating avascular necrosis.
AB - Gene delivery to bone is useful both as an experimental tool and as a potential therapeutic strategy. Among its advantages over protein delivery are the potential for directed, sustained and regulated expression of authentically processed, nascent proteins. Although no clinical trials have been initiated, there is a substantial pre-clinical literature documenting the successful transfer of genes to bone, and their intraosseous expression. Recombinant vectors derived from adenovirus, retrovirus and lentivirus, as well as non-viral vectors, have been used for this purpose. Both ex vivo and in vivo strategies, including gene-activated matrices, have been explored. Ex vivo delivery has often employed mesenchymal stem cells (MSCs), partly because of their ability to differentiate into osteoblasts. MSCs also have the potential to home to bone after systemic administration, which could serve as a useful way to deliver transgenes in a disseminated fashion for the treatment of diseases affecting the whole skeleton, such as osteoporosis or osteogenesis imperfecta. Local delivery of osteogenic transgenes, particularly those encoding bone morphogenetic proteins, has shown great promise in a number of applications where it is necessary to regenerate bone. These include healing large segmental defects in long bones and the cranium, as well as spinal fusion and treating avascular necrosis.
KW - Animal models
KW - Bone healing
KW - Facilitated endogenous repair
KW - Gene therapy
KW - Osteogenesis imperfecta
KW - Research translation
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U2 - 10.1016/j.addr.2012.03.013
DO - 10.1016/j.addr.2012.03.013
M3 - Review article
C2 - 22480730
AN - SCOPUS:84865330310
SN - 0169-409X
VL - 64
SP - 1331
EP - 1340
JO - Advanced Drug Delivery Reviews
JF - Advanced Drug Delivery Reviews
IS - 12
ER -