1. Gene editing removes barrier to pig-to-human organ transplant

Gene editing removes barrier to pig-to-human organ transplant

Scientists have overcome a major hurdle for humans to receive life-saving organ transplants from pigs, thanks to a powerful new gene-editing technique.

By: | Updated: October 16, 2015 9:10 AM

Scientists have overcome a major hurdle for humans to receive life-saving organ transplants from pigs, thanks to a powerful new gene-editing technique.

Never before have scientists been able to make scores of simultaneous genetic edits to an organism’s genome.

But now in a new study the gene editing system known as “CRISPRu2013Cas9” has been used to genetically engineer pig DNA in 62 locations – an explosive leap forward in CRISPR’s capability when compared to its previous record maximum of just six simultaneous edits.

The 62 edits were executed by researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University and Harvard Medical School to inactivate retroviruses found natively in the pig genome that has so far inhibited pig organs from being suitable for transplant in human patients.

With the retroviruses safely removed via genetic engineering, however, the road is now open towards the possibility that humans could one day receive lifeu2013saving organ transplants from pigs, researchers said.

The concept of xenotransplantation, which is the transplant of an organ from one species to another, is nothing new.

Pigs in particular have been especially promising candidates due to their similar size and physiology to humans.

In fact, pig heart valves are already commonly sterilised and deu2013cellularised for repairing or replacing human heart valves.

But the transplant of whole, functional organs comprised of living cells and tissue constructs has presented a unique set of challenges for scientists.

One of the primary problems 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 presence of this type of virus found in pigs u2013 known as porcine endogenous retroviruses or PERVs u2013 brought over a billion of dollars of pharmaceutical industry investments into developing xenotransplant methods to a standstill by the early 2000s,” said George Church, Professor of Genetics at Harvard Medical School (HMS).

“PERVs and the lack of ability to remove them from pig DNA was a real showstopper on what had been a promising stage set for xenotransplantation,” said Church.

Using CRISPRu2013Cas9 like a pair of molecular scissors, Church and his team have inactivated all 62 repetitive genes containing a PERV in pig DNA, surpassing a significant obstacle on the path to bringing xenotransplantation to clinical reality.

The study was published in the journal Science.

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