Pig organs were previously seen as a promising option for overcoming donor organ shortages as they are a similar size to human organs, but there is a high risk of rejection. The use of pig organs also poses an infection risk due to the presence of viral DNA in the genome which could be transmitted to human cells.
'The presence of this type of virus found in pigs – known as porcine endogenous retroviruses or PERVs – brought over a billion of dollars of pharmaceutical industry investments into developing xenotransplant methods to a standstill by the early 2000s,' said Professor George Church from the Wyss Institute in Cambridge, Massachusetts.
'PERVs and the lack of ability to remove them from pig DNA was a real showstopper on what had been a promising stage set for xenotransplantation.'
Professor Church and his team used the CRISPR/Cas9 system, which allows researchers to delete or replace specific parts of the genome. They identified 62 PERV copies in a porcine kidney epithelial cell line (PK15). Then, using CRISPR/Cas9, they successfully deactivated all 62 copies of the PERV pol gene, which is required for viral replication and infection.
When the researchers co-cultured modified PK15 cells with human embryonic kidney cells, PERV transmission to human cells was reduced more than 1000-fold than when co-cultured with unmodified PK15 cells.
The researchers, who report their findings in Science, hope that the modified pig cells could be used to clone a line of pigs with inactivated PERVs, thus removing the risk of PERV transmission and infection during xenotransplantation.
Dr Sarah Chan from the University of Edinburgh told the BBC: 'Even once the scientific and safety issues have been addressed, we should be mindful of the possible cultural concerns and societal impacts associated with more widespread use of pig organs for human transplantation.
'Nonetheless, the results of the study are valuable both as a proof of principle and a potential step towards therapeutic advances in this area of much-needed research.'