Sun. Feb 5th, 2023
Scientists debug pig genome in preparation for agricultural organ donors

After a thorough anti-virus scan, de-bugged pigs are one step closer to growing organs for us.

Researchers used the latest gene-editing technology to deactivate 25 remnants of ancient viruses called porcine endogenous retroviruses (PERVs) embedded in the DNA of a pig cell line. Pig genomes are full of lurking PERVs, which threaten to emerge and infect humans. But with a genome wiped of active viruses, the researchers produced 37 piglets that are PERV-free. The creation of those clean little fattening pigs reported on Thursday Scienceis progress toward using pigs as human organ donors, the researchers say.

“Our study highlighted the value of PERV inactivation to prevent cross-species virus transmission and demonstrated the successful production of PERV-inactivated animals to address the safety issue in clinical xenotransplantation,” the authors concluded.

Pigs have long been considered an ideal animal for hatching organs that can be transplanted into humans. Their organs are about the same size as ours and function in the same way. But there are also numerous barriers to cross-species sharing. For starters, tissue from another human — let alone another animal — is enough to startle and attack our immune system. All pig organs suitable for human transplantation would have to be carefully genetically modified to rule out such a severe immune response. Then there are other issues, such as blood clotting issues – and the PERVs.

Researchers have always been concerned about PERVs in pig-to-human transmission. The retroviruses, which are passed down from generation to pig, have never been proven to be transmitted to humans – no cases of human PERV disease have ever been reported, even in patients who have undergone tissue transplants from pigs. Still, the concern remains. And in labs, PERVs can jump from pig cells to human cells.

Hog wanted genetic engineering

Researchers saw this firsthand in the new study, led by Harvard geneticist George Church and Luhan Yang, a bioengineer and president of eGenesis, a biotech start-up she and Church co-founded. Before they wiped out PERVs from a pig cell line, they showed that PERVs from a pig cell line infected a line of human cells when researchers grew them together. And that infected line of human cells infected another line of human cells when researchers grew them together.

That was enough to convince Church, Yang and colleagues that PERVs are something they had to destroy if they wanted to use pigs as organ donors. So they turned to the flashy new gene-editing tool, CRISPER-Cas9, to splice and deactivate all instances of PERV genes in a pig cell line. They used a row of pig connective tissue cells that contained 25 PERVs. When the researchers initially tried to knock out all PERVs, they found that many cells either still had PERVs and/or were not growing normally. They speculated that the genetic cutting and dicing was enough to signal the cells that something was drastically wrong and that they should commit suicide — a cell process called apoptosis. So the researchers added a cocktail of chemicals and factors that suppressed such suicidal signals. The result was 100 percent PERV eradication.

One of the PERV-free piglets.
Enlarge / One of the PERV-free piglets.

By aspirating the virus-cleared genetic material and injecting it into the empty nuclei of pig egg cells, the researchers created embryos without PERVs. Those embryos were implanted in sows and grew into 37 piglets, 15 of which were still healthy after four months.

There is still a lot of work to be done to turn the boars into human organ factories. And it is unclear whether researchers will need PERV-free piglets for this. But for now, Church, Yang and their team believe their new pigs “could serve as a base strain of pigs, which can be further developed to provide safe and effective organ and tissue sources for xenotransplantation.”

Science2017. DOI: 10.1126/science.aan4187 (About DOIs).

By akfire1

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