RNA interference (RNAi) is a natural process through which double-stranded RNA molecules can silence the gene carrying the same code as the particular RNA of interest. In 2006, the discovery of RNAi was awarded the Nobel Prize in Medicine and its success has accumulated since. Gene silencing through RNAi has been used successfully in a broad range of diseases, and, more recently, this technique has gained interest in the field of organ transplantation. Here, genes related to ischemia-reperfusion injury (IRI) or graft rejection may be silenced to improve organ quality after transplantation. Several strategies have been used to deliver siRNA, and pretransplant machine perfusion presents a unique opportunity to deliver siRNA to the target organ during ex situ preservation. In this review, the potential of RNAi in the field of organ transplantation will be discussed. A brief overview on the discovery of RNAi, its mechanism, and limitations are included. In addition, studies using RNAi to target genes related to IRI in liver, kidney, lung, and heart transplantation are discussed.
Keywords: RNA interference; RNA therapeutics; ex situ machine perfusion; ex vivo perfusion; gene editing; gene silencing; gene therapy; graft modulation; graft pretreatment; graft treatment; ischemia-reperfusion injury (IRI); miRNA; organ preservation; organ transplantation; regenerative medicine; rejection; shRNA; siRNA; small interfering RNA (siRNA); translational research/science; transplant.
© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.