Pig-to-human organ transplants closer, thanks to gene editing
Researchers have created pigs without the built-in retroviruses that have been a significant obstacle to using pig organs for transplant to humans.
The successful transplantation of pig organs into humans has moved a significant step nearer with one of the most difficult clinical obstacles reportedly overcome.
In a paper published in the journal Science, a team led by researchers at the US biotech company eGenesis reveals that it has found a way to inactivate porcine endogenous retroviruses (PERVs) – infectious agents which are encoded into the pig genome and which can migrate across the species barrier when pig tissue is introduced into the human body.
The team, led by the company’s Dong Niu, first used a cell line to demonstrate that PERVs are not only able to migrate from pig to human cells, but can also then move between cells in their new host.
The ability of PERVs to survive in a human body raised serious questions about the efficacy and safety of using pig organs in surgery – a process known as xenotransplantation.
Niu’s team identified and mapped PERV sites on the pig genome, finding 25 in total. They then deployed CRISPR Cas-9 gene editing technology to deactivate every site.
Despite this feat, however, cloning the modified cells resulted in only 90% continued PERV-free generation – a good result, but not good enough for risk-free transplantation.
Further modifications, however, particularly in the process of DNA repair, produced a 100% PERV-free result.
“This research represents an important advance in addressing safety concerns about cross-species viral transmission,” said co-author and eGenesis chief scientific officer, Luhan Yang.
“Our team will further engineer the PERV-free pig strain to deliver safe and effective xenotransplantation."
In further research, the scientists implanted the modified cell lines into pig embryos. They report the successful births of several PERV-free piglets, although to date they have survived only to four months.