Powerful gene editing could make pigs perfect organ donors
Monday, November 02, 2015
By modifying 62 genes in pig embryos, scientists think they may have found a way to make pigs suitable organ donors for humans.
Led by Harvard Medical School geneticist George Church, the work was presented Oct. 5 at a meeting of the U.S. National Academy of Sciences. Church and his colleagues spoke about using CRISPR/Cas9 gene-editing technology to inactivate 62 porcine endogenous retroviruses (PERVs) in pig embryos. Embedded in all pigs' genomes, the viruses cannot be treated or neutralized once present in a human.
That's why pigs' organs, though similar in size, haven't yet been transplanted into human recipients. Based on laboratory tests, doctors fear the viruses would make humans who received the organs ill. PERVs have moved from pig to human cells in a dish, and have infected human cells transplanted into immune-compromised mice.
Church and his colleagues also addressed another problem with using pig organs in humans. Some pig genes cause a violent human immune response or can trigger blood clotting in human organ recipients. More than 20 genes in a separate set of pig embryos were modified to combat this problem.
If pig organs are to ever be successfully used in human recipients, both the gene modifications and the PERV deletions will be necessary. Church has co-founded a biotech firm called eGenesis and secured lab space at Harvard's medical school.
While few details have been released, Church says the company intends to produce pigs with the sole purpose of organ transplantation. Both sets of embryos with modified genes — the ones with PERV deletion and the ones with the protein-encoding modification — are nearly ready to be implanted into mother pigs.
"This is something I've been wanting to do for almost a decade," Church said in Nature magazine.
With the new gene modifications, the idea of xenotransplantation — using animal organs in humans — could be revived.
"Basically, this whole field has been in the doldrums for 15 years," Church told Science magazine. "There's been kind of a few true believers that had it on life support. But I think this changes the game completely."
Even with eliminating the PERV problem, there are factors that must be addressed before pigs can become viable human donors.
Daniel Salomon, a transplant immunologist and physician at Scripps Research Institute in San Diego, California, says the other molecules in pig cells that cause the human immune system to reject them must be identified and modified in a way that doesn't kill the pig.
Church acknowledged this, saying he and his team had a list of pig molecules that must be addressed using CRISPR and other methods. The team hopes to have PERV-free, immune-friendly pig embryos ready to implant in mother pigs in 2016.
Even so, some researchers say the U.S. Food and Drug Administration is another possible stumbling block for xenotransplantation efforts. However, Salomon who once led an FDA panel on the risks of cross-species transplants, says research being done to reduce organ rejection could help move things along.
"I'm not freaked out about PERV anymore," Salomon said. But "if you can reduce by 1,000-fold the potential of PERV transmission, you should do it."
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