alexa Osteoinductive applications of regional gene therapy: ex vivo gene transfer.
Dentistry

Dentistry

Dentistry

Author(s): Oakes DA, Lieberman JR

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Abstract Gene therapy represents the new frontier of medical science. Currently, there are no completely satisfactory treatment options for bone repair problems such as fracture nonunion, revision total joint arthroplasty, tumor resections, and fusions of the spine. Autogenous bone grafts, allograft implants, and prosthetic implants have been used to treat these problems. However, there are significant limitations associated with these methods including limited supply and limited osteogenic potential. Gene therapy, involving the manipulation of endogenous cells to generate specific proteins, offers a potential solution for these problems. By transferring genes into cells at a specific anatomic site, the osteoinductive properties of growth factors can be used at physiologic doses for a sustained period to facilitate a more significant healing response. Successful gene therapy involves four key steps: transduction, transcription, translation, and expression. To achieve gene transduction of a target cell, gene therapy models use vectors to enhance the entry and expression of exogenous deoxyribonucleic acid into the target cell's nucleus. The transduction of a gene can be performed via either an ex vivo or an in vivo approach. Although there are many potential target cells for gene therapy, the specific anatomic site, the quality of the bone, and the soft-tissue envelope, will influence the selection of the target cells for regional gene therapy. Gene therapy vectors delivered to a treatment site in osteoconductive carriers have yielded promising results. Several investigators have shown exciting results using ex vivo and in vivo regional gene therapy in animal models. Comparative studies and human clinical trials have not yet been performed but are necessary to identify the optimal genes and dosages for each specific application of regional gene therapy. In the future, the treatment options for bone loss problems will represent a clinical continuum based on the anatomic site, the condition of the target tissue bed, and the desired duration of protein production.
This article was published in Clin Orthop Relat Res and referenced in Dentistry

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