Public Release: 

Virally cleansing the pig genome

American Association for the Advancement of Science

This news release is available in Japanese.

In effort to enable organ transplants into humans, researchers have used the CRISPR gene editing technique to inactivate all 62 copies of a retrovirus in a pig cell line, a significant step on the road to generating pig organs for possible xenotransplantation. Worldwide, human organs for transplant are in short supply. While pig organs have been considered a viable option, porcine endogenous retroviruses (or PERVs) -- found in all pigs' DNA - can be transmitted to humans where they may cause disease. This has resulted in a worldwide moratorium on pig-to-human transplants. Prior strategies for reducing the risk of PERV transmission to humans during transplantation have had limited success. Here, George Church and colleagues report the successful use of the CRISPR-Cas9 RNA-guided nuclease system to inactivate a PERV gene called pol critical for the retrovirus's replication. The researchers determined 62 copies of the retrovirus to be present in pig epithelial cells and designed two Cas9 guide RNAs that targeted the pol gene on each one. They next examined whether their engineered pig cells could eliminate transmission of the retrovirus to human cells in vitro, finding PERV infectivity was reduced by up to a thousand fold. Critically, the Cas9-based genome engineering strategy did not appear to cause genomic rearrangements. Future work in pig embryonic cell lines is needed to develop genetically modified pigs to grow organs for human transplantation, the authors say.

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**For Immediate Release**

Article #26: "Genome-wide inactivation of porcine endogenous retroviruses (PERVs)," by L. Yang; M. Güell; D. Niu; H. George; E. Lesha; D. Grishin; J. Aach; E. Shrock; W. Xu; J. Poci; R. Cortazio; G. Church at Harvard Medical School in Boston, MA; L. Yang; M. Güell; G. Church at Wyss Institute for Biologically Inspired Engineering in Cambridge, MA; L. Yang; M. Güell; G. Church at eGenesis Biosciences in Boston, MA; D. Niu at Zhejiang University in Hangzhou, China; W. Xu; R.A. Wilkinson; J.A. Fishman at Massachusetts General Hospital in Boston, MA.

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