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Rewriting Life

CRISPR Opens Up New Possibilities for Transplants Using Pig Organs

Scientists have bred gene-edited pigs free of viruses that pose a potential health risk for humans.

These baby pigs were the first to be born without innate viruses in their DNA.

In a step toward making pigs suitable organ donors for humans, researchers at a startup company called eGenesis have for the first time used gene editing to eliminate a family of viruses in pigs that can be transmitted to people. This step could make pig organs safer for human use.

In the U.S. alone, more than 116,000 people are waiting to receive a lifesaving organ transplant, while only 17,157 transplants have been performed this year, according to the U.S. Department of Health and Human Services.

For decades, xenotransplantation—that is, transplanting animal organs into people—has been seen as one possible way to ease the human organ shortage. But almost all attempts to implant animal organs into people have failed. In 1984, “Baby Fae” famously received a heart transplant from a baboon and died 20 days later.

Scientists have since turned their interest to pigs, which have organs similar in size to humans’. They can also be bred easily and in large numbers. The problem is that humans are even more biologically different from pigs than they are from baboons. Pig organs are quickly rejected by the body, causing severe immune reactions. The viruses the researchers targeted—known as porcine endogenous retroviruses, or PERVs—have been another concern. The viruses dwell in pig DNA and can be passed down during transplantation and infect human cells.

Now eGenesis, spun out of Harvard geneticist George Church’s lab, may have figured out how to get rid of these species-jumping viruses. Luhan Yang, cofounder and chief scientific officer at eGenesis, says her team wanted to deactivate this group of viruses to see if the pigs would develop normally.

Using the gene-editing tool CRISPR, Yang and her team were able to disable all 25 copies of the viruses in pig embryos. They then implanted the embryos into female pigs, which gave birth to piglets that didn’t harbor the viruses. The company has produced 37 pigs this way and has been monitoring them for four months. So far, the resulting animals are healthy and virus-free. The results appear today in the journal Science.

Muhammad Mohiuddin, a professor of surgery and director of the xenotransplantation program at the University of Maryland School of Medicine, who was not involved in the study, says cutting multiple genes at once with CRISPR saves a lot of time over conventional genetic engineering. But while these viruses may be able to infect human tissue, he says there’s no evidence yet that they actually cause health problems in people.

“There are other issues that will limit the clinical application of xenotransplantation other than these viruses,” says Mohiuddin, referring to the immune response the body generates against a transplanted animal organ.

Yang says eGenesis is also using CRISPR to make modifications to genes involved in the immune system. However, she says human tests of an organ produced in one of these gene-edited pigs are still years away.

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These baby pigs were the first to be born without innate viruses in their DNA.
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