Science magazine mulls over new research showing how CRISPR gene editing successfully got rid of PERVs – porcine endogenous retroviruses – and made it that much easier to take a heart, liver, lung or kidney out of a pig and put it into a human being in need:
“If this is correct, it’s a great achievement,” says virologist Joachim Denner of the Robert Koch Institute in Berlin who has studied the mysterious PERV sequences. Scientists still don’t know whether the viral particles they produce can infect humans at all, he notes, much less whether they would cause disease if they did. And even with PERVs off the table, pigs will require other modifications so that their organs won’t be rejected by the human immune system or cause other harms.
Two early developers of that gene-editing technology, Harvard University geneticists George Church and Luhan Yang, suspected that CRISPR’s highly efficient duo of guide RNA and a DNA-slicing enzyme could make precise, genome-wide changes to pig cells. In 2015, they co-founded the company eGenesis to focus on engineering transplantable organs, and Yang became the company’s chief scientific officer. The same year, they showed that CRISPR could knock out PERV genes at all 62 sites in the pig genome—the most widespread CRISPR editing feat to date.
But for that project, the researchers had used a line of “immortal” pig kidney cells, chosen for their ability to survive and divide indefinitely in a dish. To make PERV-free pigs, they needed to start with genetically normal cells straight from a living pig. In the new work, done with a team of Danish and Chinese collaborators, the eGenesis team applied the CRISPR system to cells derived from the connective tissue of fetal pigs. Those cells proved more fragile when subjected to CRISPR’s hack job: Once edited, they failed to grow normally, possibly because the damage to their DNA prompted them to stop dividing or self-destruct, Yang says. But by exposing the cells to a chemical cocktail that encouraged growth and tamped down on a key growth-suppressing gene, the team bumped up the portion of flourishing PERV-free cells in a dish to 100%.
“At this moment, I don’t think we are very worried about PERV,” adds Muhammad Mohiuddin, a cardiac transplant surgeon at the University of Maryland School of Medicine in Baltimore. His group is collaborating with the company United Therapeutics to develop implantable pig hearts. (He is gearing up to swap them into the chests of baboons, after showing last year that the organs could survive for years beating in baboons’ abdomens.)