Researchers are trying to make pig organs more viable for transplant

Harvard geneticist George Church

In one study, scientists created piglets that no longer have active genes for a pig virus, a key step in making their organs suitable for transplant in humans.

The team used CRISPR gene-editing technology to remove some retroviruses from a pig's DNA, and then cloned that pig to produce multiple small piglets with virus-free organs. These are known as endogenous retroviruses which, although normally silent, can be activated to become fully infectious for human cells when pig cells carrying these retroviruses are co-incubated with human cells.

People with compromised immune systems could be particularly at risk from these retroviruses, as the viral DNA would more easily proliferate through their cells, but editing genes using the scientists' method may solve that problem. Pig organs, however, are quickly rejected by the human body, hence the push to make them more compatible.

The United Network for Organ Sharing says the list of people who need an organ to save their lives is in the tens of thousands, with kidneys representing the greatest need.

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Using the gene-editing tool CRISPR, Yang and her team were able to disable 25 copies of these viruses in pig embryos. 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.

Research in xenotransplantation - that's the concept of transplanting organs from other species into humans - has always run into issues with the human immune system, which, perhaps not surprisingly, recognizes pig parts as foreign and attacks them with all their might. Recent gene editing advances, however, are rejuvenating interest in pig-to-human transplants. "Our animal is probably the most [genetically] modified animal on the Earth", says Luhan Yang, co-founder and chief science officer of eGenesis, the Cambridge, Mass. -based start-up that led the research. Pigs are the biggest animals that have undergone CRISPR, he says, and he wants to see what happens when they are allowed to "grow to a ripe old age" of over 20. "I fail to understand the significance of this [infectivity] unless it is shown that it can cause some kind of disease". Still, Denner says, "If it is possible to knock [PERVs] out, you should do it".

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. But one of the largest safety concerns has been the fact that most mammals including pigs contain repetitive, latent retrovirus fragments in their genomes - present in all their living cells - that are harmless to their native hosts but can cause disease in other species. The embryos were implanted in sows and grew into piglets that were genetically identical to the pig that supplied the initial cell.

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