Recombinant adenoviral mediated gene transfer in ischemic impaired wound healing

Chronic nonhealing wounds represent a large clinical problem resulting in s evere disabilities and large healthcare expenditures. Despite the scope of this problem, effective new therapies are lacking. The deficiency of growth factors in chronic wounds has brought attention to the topical application of growth factors, but initial clinical trials have resulted in only modes t improvements in healing despite large, repetitive doses. The modest impro vement in healing observed in these trials show that growth factors can imp rove chronic wound healing, but a better means of growth factor delivery is needed. We hypothesized that gene therapy using a recombinant adenoviral v ector could be used to induce transgene production directly by cells in the wound. An adenovirus containing the beta-galactosidase reporter transgene (Ad-LacZ) was used in the ischemic rabbit ear model to test this hypothesis . Ad-LacZ resulted in efficient transgene delivery to cells participating i n the wound healing response, with expression up to 2 weeks. However, wound reepithelialization was impaired in Ad-LacZ treated wounds compared to veh icle control wounds, Adenoviral mediated gene transfer is a promising effic ient means of growth factor delivery to chronic wounds. However, selection of the proper transgene with appropriate biologic activity in wound healing may be essential to overcome the potential adverse effects of adenoviral i nfection.