The race to create pigs with organs that are suitable for transplanting into people is hotting up. At least three teams have added human genes to pigs to try to prevent donor organs from being rejected by a recipient’s immune system.
There is a shortage of human donor organs. Transplanting organs from pigs to humans could solve this, but organs from normal pigs trigger a very strong attack from the immune system.
Different research teams are trying to tackle this by adding human genes to pigs, in an effort to make their organs suitable for humans, and potentially less likely to be rejected by the recipient’s immune system too.
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Lijin Zou at the First Affiliated Hospital of Nanchang University in China and his colleagues into which they added eight human genes that reduce the chance of a donor organ being rejected, and removed three key pig genes that trigger organ rejection.
The group then transplanted skin from these pigs to monkeys. The skin graft survived for up to 25 days without the monkeys needing any immune system suppressing drugs.
“So far, it is the best result, at least from the English literature,” says Zou. His team is preparing to start human trials of the pig skin as a temporary cover for extensive burns. These are usually covered with skin from dead human donors while new skin grows. Zou says he would “expect even better” results in humans.
Genome changes
Interest in this approach has surged in the past decade as advances such as CRISPR gene editing have made it feasible to make extensive changes to the genomes of animals.
In December, Luhan Yang at biotech firms Qihan Bio in China and eGenesis in the US with nine added human genes and dozens of deleted pig genes.
In addition to deleting the same three genes knocked out by Zou’s team, Yang’s team also inactivated dozens of pig viral genes known as porcine endogenous retroviruses, or PERVs.
“It is a major technological achievement,” says David Cooper of the University of Alabama at Birmingham, a former transplant surgeon who works on transplanting pig organs. But regulators will want to know whether all of these genetic changes are necessary, he says.
Cooper is working with , which has added six human genes to pigs, as well as deleting the same three pig genes as the other teams. “I believe that any of these pigs will be suitable for a clinical trial [in humans], but we have to persuade the regulatory authorities first,” he says.
If PERVs start infecting human cells after a transplant, there is a risk they might cause cancer years later, says John Coffin at Tufts University School of Medicine in Boston. But this is still better than the outcomes if people don’t get a transplant, he says.
Reference: bioRxiv, DOI: ,
Article amended on 30 January 2020
We have clarified the organ transplant process.
