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Genome-wide inactivation of porcine endogenous retroviruses (PERVs)

Science  27 Nov 2015:
Vol. 350, Issue 6264, pp. 1101-1104
DOI: 10.1126/science.aad1191

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Virally cleansing the pig genome

Transplants from pigs could be a solution to a shortage of human organs for transplantation. Unfortunately, porcine endogenous retroviruses (PERVs) are rife in pigs and can be transmitted to humans, risking disease. L. Yang et al. integrated CRISPR-Cas into the pig cell genome, where continuous induction of the Cas9 editing enzyme resulted in the mutation of every single PERV reverse transcriptase gene. This prevented replication of all copies of PERV, viral infection, and transmission to human cells.

Science, this issue p. 1101

Abstract

The shortage of organs for transplantation is a major barrier to the treatment of organ failure. Although porcine organs are considered promising, their use has been checked by concerns about the transmission of porcine endogenous retroviruses (PERVs) to humans. Here we describe the eradication of all PERVs in a porcine kidney epithelial cell line (PK15). We first determined the PK15 PERV copy number to be 62. Using CRISPR-Cas9, we disrupted all copies of the PERV pol gene and demonstrated a >1000-fold reduction in PERV transmission to human cells, using our engineered cells. Our study shows that CRISPR-Cas9 multiplexability can be as high as 62 and demonstrates the possibility that PERVs can be inactivated for clinical application of porcine-to-human xenotransplantation.

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