Abstract
Gene therapy is a rapidly developing field, finally yielding clinical benefits. Genetic engineering of organs for transplantation may soon be an option, thanks to convergence with another breakthrough technology, ex vivo machine perfusion (EVMP). EVMP allows access to the functioning organ for genetic manipulation prior to transplant. EVMP has the potential to enhance genetic engineering efficiency, improve graft survival, and reduce posttransplant complications. This will enable genetic modifications with a vast variety of applications, while raising questions on the ethics and regulation of this emerging technology. This review provides an in-depth discussion of current methodologies for delivering genetic vectors to transplantable organs, particularly focusing on the enabling role of EVMP. Organ-by-organ analysis and key characteristics of various vector and treatment options are assessed. We offer a road map for research and clinical translation, arguing that achieving scientific benchmarks while creating anticipatory governance is necessary to secure societal benefit from this technology.