In vitro Ad5F35-mediated CTLA4-Ig gene transfer prolongs pig skin xenotransplant survival

Wound closure and coverage are the biggest challenges faced by medical practitioners in treating severe burns. Fresh cadaver allografts are still considered to be the gold standard skin substitute. Unfortunately, their use is severely impeded by inadequate availability. In this report we endeavored to solve this problem by using gene-modified pig skin as a substitute for human skin. We report that adenovirus (Ad)-mediated transfer of human cytotoxic T-lymphocyte-associated antigen 4 immunoglobin (CTLA4-Ig) into pig skin in vitro is a useful approach to lower immunostimulatory ability and improve the take of pig skin for wound coverage. To optimize gene transfer efficiency, we also compared exogenous gene transfer efficiency in pig skin by Ad5F35 vector with that of the widely used Ad5. The uptake efficiency of Ad5F35 was about 1.3 times more than that of Ad5, and the survival time on rat burn wounds was prolonged by about 3 days. Our results demonstrate that CTLA4Ig gene-modified pig skin is a promising biologic dressing for wound coverage and Ad5F35 an effective viral carrier for delivery.