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Gene therapy approaches to regenerating bone

Skeletal Biotech Laboratory, The Hebrew University, Hadassah Faculty of Dental Medicine, Ein Kerem, Jerusalem, Israel.
Advanced drug delivery reviews (Impact Factor: 12.71). 03/2012; 64(12):1320-30. DOI: 10.1016/j.addr.2012.03.007
Source: PubMed

ABSTRACT Bone formation and regeneration therapies continue to require optimization and improvement because many skeletal disorders remain undertreated. Clinical solutions to nonunion fractures and osteoporotic vertebral compression fractures, for example, remain suboptimal and better therapeutic approaches must be created. The widespread use of recombinant human bone morphogenetic proteins (rhBMPs) for spine fusion was recently questioned by a series of reports in a special issue of The Spine Journal, which elucidated the side effects and complications of direct rhBMP treatments. Gene therapy - both direct (in vivo) and cell-mediated (ex vivo) - has long been studied extensively to provide much needed improvements in bone regeneration. In this article, we review recent advances in gene therapy research whose aims are in vivo or ex vivo bone regeneration or formation. We examine appropriate vectors, safety issues, and rates of bone formation. The use of animal models and their relevance for translation of research results to the clinical setting are also discussed in order to provide the reader with a critical view. Finally, we elucidate the main challenges and hurdles faced by gene therapy aimed at bone regeneration as well as expected future trends in this field.

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    • "In addition, the overwhelming amount of studies that have been investigating the molecular scenario orchestrating osteogenesis and bone healing, provided new osteoinductive molecules to be tested as potential drugs in spine surgery. On the other hand, cell-based gene therapy approaches based on engineered-osteoinductive cells allowed achieving the most convincing results in terms of bone healing and spine fusion in animal models [14] [15] [16] [17] [18] [19]. Actually, genetically engineered cells are believed to maintain physiologic doses of a gene product for a sustained period once inoculated into the selected anatomical site, facilitating an efficient bone healing [20]. "
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    The Scientific World Journal 01/2014; 2014(406159):406159. DOI:10.1155/2014/406159 · 1.73 Impact Factor
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    • "e l s e v i e r. co m/ lo ca t e / b i o m a t e ri a l s regardless of the treatment regimen, dose, or delivery method. The second strategy utilizes viral and/or non-viral targeted osteogenic or angiogenic gene delivery approaches [16] [17]. While a few of the gene transfer methods for critical defect healing have reached orthopedic pre-clinical trials, there remain significant regulatory, efficacy , and safety concerns with the use of viral agents or genetically altered cells for implantation into patients. "
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