Transgenic pigs for xenotransplantation: selection of promoter sequences for reliable transgene expression

Abstract

Appropriate expression of immunomodulatory and anticoagulant proteins on endothelial cells is essential to prevent rejection of vascularized porcine organs after transplantation into primates. Here, we review the promoter sequences used for the establishment of transgenic pigs, as organ donors for xenotransplantation. Transgenic pigs were produced using viral, chicken, mouse, human, and porcine promoter sequences with ubiquitous or cell type-specific activity. In addition to the expression of human complement regulatory proteins, which were efficient to prevent hyperacute rejection of pig-to-primate xenografts, novel transgenes, targeting cellular rejection mechanisms, abnormal-blood coagulation, or the risk of viral transmission, have been published or announced in preliminary reports. Accurate spatiotemporal expression of immunomodulatory and anticoagulant proteins on the endothelial cells of transgenic pigs is required for the successful xenotransplantation of vascularized organs into primates. Targeting transgene expression specifically to the cells critical for xenograft rejection may eliminate potential side effects of ubiquitous expression. Comparison of regulatory sequences from various species indicates that carefully selected porcine promoter sequences may be beneficial to achieve this aim.