The radioprotection of composite tissue free flaps using ex vivo gene therapy. (360G-Wellcome-098937_Z_12_Z)

Radiotherapy forms a vital component of the adjuvant management of cancer following ablative surgery and has been shown to confer a survival benefit by controlling local disease. When reconstruction is required after radical excision this is usually in the form of a free flap, where a flap (composite block of tissue supplied by a named blood vessel) is moved with its vascular pedicle from a donor site to a recipient bed. Irradiation of free flaps results in fibrosis, fat necrosis and flap contra cture, leading to anatomical distortion, wound breakdown and often necessitates surgical debridement and salvage reconstruction. A delayed reconstruction may be performed after radiotherapy but means more operative procedures, worse aesthetic outcomes and can be psychologically deleterious to the disfigured patient. Radioprotecting a free flap offers patients requiring reconstruction the opportunity to have an earlier and more durable reconstruction by selectively abrogating the deleterious effects of radiotherapy on flap tissues only. We propose to achieve this by modulating two pathways (SOD2 and connective tissue growth factor (CTGF)) that have already shown promise in ameliorating the cellular damage caused by radiotherapy. We aim to achieve this using a lentiviral vector to produce longer lasting expression of transgene products in vivo.