One way to help the many people that wait on transplant lists for an available organ would be to grow new ones. Some researchers have suggested using an animal like the pig for such a purpose, but retroviruses lurking in the pig genome might pose a problem before that can happen. Now scientists have successfully made edits to the pig genome, silencing those retroviruses. While there is still a lot more work remaining before organs for transplantation can be used in human patients, this is a big step forward.
Porcine endogenous retroviruses, or PERVs, can be transmitted from pig cells to other cells when they are grown together. While it had been shown that it was possible to remove the genes driving the virus from the genome in cell culture, only now has it been demonstrated in living animals.
Researchers George Church, Dong Niu, and colleagues were the first to show that PERVs infect human cells when cultured with pig cells. When PERV-infected human cells were exposed to uninfected human cells, the virus spread to those uninfected cells, showing that eliminating these viruses before transplantation of organs from pigs to humans might be important before transplantation of pig-derived organs.
It’s not known what might happen to a person who got an organ that contained PERVs. No one is interested in using a human to find out though. Additional changes would also have to be made to the pig genome so it would not set off alarms in the human immune system.
As a good proof-of-concept, the researchers were able to use the CRISPR gene editing tool to deactivate PERV genes they identified and characterized. Reporting in Science, there were 25 total genes in pig fibroblast cells, and after the editing was performed, the scientists had to supply some additional modifications to achieve 100% deactivation of PERVs. After implanting modified embryos into sows, piglets were born with no sign of PERVs. Some of the piglets survived for five months.
However, some scientists think that if PERVs have to be completely deactivated, it presents a new hurdle to researchers already facing enormous challenges. “If this is required, it will add to the time before pigs can be used for transplants in patients in desperate need,” transplant immunologist David Cooper of the University of Alabama at Birmingham told Science News. “And it will add to the cost of providing pigs for the initial clinical trials.”
Other researchers aren’t convinced it was necessary. “At this moment, I don’t think we are very worried about PERV,” commented Muhammad Mohiuddin, a cardiac transplant surgeon at the University of Maryland School of Medicine in Baltimore who is working to develop implantable pig hearts. He will be taking cues from regulatory agencies. “If FDA mandates us, ‘To move forward you need to get rid of this PERV since George Church has shown you how to do it, then of course, yes,” he said.
Compatibility with the human immune system may still be the biggest obstacle to developing pig organs for human transplant. Several research groups are trying to tackle that problem.
Sources: Science Daily via AAAS, Science News, Science
