FGF2-targeted adenovirus encoding platelet-derived growth factor-B enhances de Novo tissue formation

Gene therapy has yet to achieve reproducible clinical efficacy, due to inad equate gene delivery, inadequate gene expression, or dose-limiting toxicity . We have developed a gene therapy technology for tissue repair and regener ation that employs a structural matrix for DNA delivery. The matrix holds t he DNA vector at the treatment site and provides a scaffolding for in-growt h and accumulation of repair cells and efficient DNA transfection. We now r eport, for the first time, matrix-mediated delivery of targeted DNA vectors for soft tissue repair. A collagen matrix was used to deliver an adenovira l vector encoding platelet-derived growth factor-B (AdPDGF-B), resulting in efficient transgene expression in vitro and in vivo. Increases in the over all levels of expression and in the relative amounts of secreted PDGF-BB we re achieved when AdPDGF-B was conjugated to fibroblast growth factor (FGF2) such that the virus was targeted for cellular uptake via FGF receptors. Ma trix-mediated delivery of AdPDGF-B enhanced wound healing responses in vivo , and FGF2 targeting generated effects comparable to nontargeted vectors at significantly lower doses. Therefore, matrix-mediated delivery in combinat ion with FGF2 targeting overcomes some of the safety and efficacy limitatio ns of current gene therapy strategies and is an attractive therapeutic appr oach for tissue repair and regeneration.