Inhibition of porcine endogenous retroviruses by RNA interference: increasing the safety of xenotransplantation

AbstractTransplantation of porcine xenografts into human recipients is a realistic option to overcome the growing worldwide shortage of suitable allogeneic organs. However, there remains the risk of infection by porcine endogenous retroviruses (PERVs) that cannot be eliminated like that by other microorganisms by breeding pigs under specified pathogen-free conditions. To reduce the release of PERVs by porcine transplants, a new approach, RNA interference (RNAi), was applied. Here, we show significant reduction of PERV expression by synthetic short interfering RNAs (siRNAs) corresponding to different parts of the viral genes gag, pol, and env. The most inhibitory sequences were selected and expressed as short hairpin RNAs (shRNAs) by a polymerase III vector system leading to persistent suppression of PERV replication. Cells or organs from transgenic pigs producing such shRNAs should increase the safety of xenotransplantation