Concerns over the transmission of porcine endogenous retroviruses (PERVs) to humans are a major barrier to the use of porcine organs in transplantation. In a new study, Yang et al. used the CRISPR–Cas9 system to simultaneously inactivate the pol genes of all 62 PERVs identified within a porcine kidney epithelial cell line. Remarkably, co-culturing of porcine and human cell lines revealed a greater than 1,000-fold decrease in the transmission of PERVs to human cells from engineered cells, compared to wild-type porcine cells.