How turning off viruses in piglets could make their organs safer for people

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In an effort to make pig organs safer for humans, scientists have successfully edited the animal’s genome to deactivate viruses that could be harmful to people. The research is an important step forward in the quest to make pig organs safe for transplantation — a dream that has kept scientists busy for decades and has the potential to save thousands of lives.

The researchers, including famous Harvard geneticist George Church, used the powerful gene-editing tool CRISPR-Cas9 and the same technology used to clone Dolly the sheep to create healthy piglets that can’t transmit harmful viruses. This doesn’t mean that pig organs are ready for humans just yet, but the study, published today in Science, raises hopes that the technology is finally ready to make animal organs fit for people.

The world has a big organ shortage problem: almost 120,000 people are currently waiting for a transplant in the US, and more than 20 people die each day waiting for a new organ. For decades, scientists have thought animals could solve the problem. But transplanting a baboon kidney or a pig heart into a person — also called xenotransplantation — has drawbacks. For example, the person’s immune system can reject the animal organ, leading to death. The other problem is the risk for infection: the pig genome is riddled with infectious agents called porcine endogenous retroviruses, or PERVs. These PERVs have the potential to infect humans if a pig organ is transplanted into a person, possibly causing tumors or leukemia.

In 2015, Church and other scientists involved in today’s research showed that they could eliminate all 62 copies of a PERV gene in pig cells using CRISPR. In this latest study, the team brought the research a step further: first, they demonstrated that PERVs in pig cells can be transmitted to human cells in a petri dish, and that infected human cells can then transmit PERVs to other healthy human cells. “Our study highlights the real concern and the significance of addressing this issue,” study co-author Luhan Yang, the co-founder of biotech company eGenesis, tells The Verge.

The researchers mapped the PERVs interwoven into the genome of pig connective tissue cells, called fibroblasts. Then, the researchers used CRISPR to edit the viral genome at 25 sites and deactivate the PERVs, so that they can’t infect cells. Finally, they used the edited cells to create embryos that were implanted into surrogate sows. (That’s the same technique used to clone Dolly.) This way, they were able to grow “designer piglets” whose PERVs are inactivated and harmless.

“We got perfectly healthy piglets,” Church tells The Verge, “so that’s amazing.” Church says it was a “pleasant surprise” to discover that the edited piglets didn’t get re-infected when growing inside a PERVs-infected mother. Some of these piglets are still growing, says Yang, and they’re still healthy. That means their organs wouldn’t risk infecting humans if transplanted. The research is basically a “safety check,” says Pablo Ross, a geneticist at the University of California, Davis, who did not take part in the study. “It removes the potential risk for cross-species transmission of these retroviruses.”

However, there’s no way those pig organs could actually be transplanted just yet, Ross says. That’s because there’s another major problem with xenotransplantation that this paper doesn’t address: the danger of organ rejection. Unless the pig organs are edited to also be more compatible for human bodies, it’d be too dangerous to transplant them into people. Church says his lab is already doing work on that, and expects to publish a paper on it soon.

In the meantime, the designer piglets should continue to be studied to make sure they stay healthy. CRISPR is known to sometimes cut pieces of DNA it wasn’t programmed to, and that could have negative health consequences. “Even with a viable piglet, we cannot be sure there were no off target effects until the pigs are extensively studied for physiological and behavior changes,” William Muir, a professor of animal sciences at Purdue University, who wasn’t involved in the research, writes in an email to The Verge. Luhan says the pigs will undergo “very stringent tests” to make sure the editing technique has worked as intended.

Still, the research is “very exciting,” Muir says, and it holds the potential to save “hundreds of lives a year.” Church says that clinical trials with engineered pig organs could begin within 10 years. And for Yang, and the company eGenesis, that would be an even more concrete step toward a lifelong goal: “We want to create a world where there is no organ shortage,” she says.

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