Potential role of direct adenoviral gene transfer in enhancing fracture repair

Gene therapy has much to offer in the treatment of conditions in which it i s necessary to increase the formation of bone, Nonunions, segmental defects , and aseptic loosening are examples of conditions where the local expressi on of genes that inhibit osteolysis and promote osteogenesis might be helpf ul, Studies in which one such possibility has been evaluated experimentally are described. These investigations used a surgically produced segmental d efect in the femurs of New Zealand White rabbits as the model system. Adjac ent muscle was fashioned around the defect to form a chamber into which ade noviral vectors were injected, High levels of transgene expression were fou nd in the muscle surrounding the defect after injection of vectors carrying marker genes. Transgene expression also was seen in the cut ends of the bo ne and the scar tissue within the gap. No transgene expression was seen in the contralateral limb, spleen, or lung; transient, low levels of expressio n were found in the liver. Transgene expression declined with time, disappe aring from all tissue but bone by Day 26; expression persisted in bone for at least 6 weeks, The control defects did not heal spontaneously, Injection of adenovirus carrying a human bone morphogenetic protein-2 complementary deoxyribonucleic acid led to healing of the segmental defect within 12 week s, as judged by radiographic, histologic, and biomechanical criteria. Adeno virus carrying a human transforming growth factor-beta 1 complementary deox yribonucleic acid showed signs of improved healing, but not to the extent s een with the bone morphogenetic protein-2 complementary deoxyribonucleic ac id, This approach to therapy holds much promise as a novel means of promoti ng osteogenesis.