Matrix-enabled gene transfer for cutaneous wound repair

Several growth factor proteins have been evaluated as therapeutic agents fo r the treatment of chronic dermal wounds. Unfortunately, most have failed t o produce significant improvements in wound healing, in part due to ineffec tive delivery and poor retention in the wound defect. It has been proposed that gene therapy might overcome the limitations of protein therapy via ong oing transcription and translation, thus prolonging the availability of the therapeutic protein. Reasoning that it would be of further benefit to ensu re retention of the DNA vector as well as the therapeutic protein within th e wound defect. we have evaluated matrix-enabled gene transfer for cutaneou s wound repair (Gene Activated Matrix). Formulations consisting of bovine t ype I collagen mixed with adenoviral or plasmid gene vectors have been eval uated in 3 in vivo models. The therapeutic transgenes employed encode human platelet derived growth factor-A or -B, proteins key to each phase of norm al wound repair. Increased granulation tissue formation, vascularization, a nd reepithelialization have been shown compared to controls treated with co llagen alone or collagen containing a reporter gene vector. Further enhance ments of the tissue repair response have been achieved by combining matrix- enabled gene transfer with molecular targeting, in which the DIVA vector is conjugated to a growth factor ligand (basic fibroblast growth factor). The se promising results support the clinical evaluation of gene activated matr ices for the treatment of chronic dermal wounds.