The use of growth factors for wound treatment has produced only minimal clinical benefit. One difficulty is achieving adequate therapeutic levels at wound sites for prolonged times. Gene therapy offers a solution to this problem by allowing for sustained growth factor production. Previously, we developed a method to redirect adenoviral vector tropism to fibroblast growth factor (FGF) receptors, allowing for their delivery to activated and proliferating cells such as those present in wounds. We now propose to apply this approach to wound healing, and to augment the retention of growth factors by delivering vectors within collagen gels.
Specific Aim #1 will expand upon preliminary in vitro data to characterize cellular production and release of platelet derived growth factor (PDGF), our primary therapeutic candidate.
Specific Aim #2 will expand upon in vivo data to characterize PDGF production and de novo tissue formation in order to confirm the efficacy of our approach. Finally, Specific Aim #3 will examine alternative growth factors that have not been adequately assessed for wound healing efficacy using in vivo models. The data generated will establish the groundwork required for the future application of this therapeutic approach in Phase II studies and clinical trials.
These experiments will permit us to develop novel therapeutics for the treatment of acute and chronic wounds. Such wounds which cause significant morbidity and can lead to mortality. Presently, few therapeutic options allow for the augmentation of soft tissue repair, especially in patients with chronic ulcers. The use of targeted gene therapy and semi- solid matrices offer the possibility of delivering novel and potent therapeutic agents, with improved specificity and retention offer existing treatments.
| Doukas, J; Chandler, L A; Gonzalez, A M et al. (2001) Matrix immobilization enhances the tissue repair activity of growth factor gene therapy vectors. Hum Gene Ther 12:783-98 |
