CRISPR Gene Editing and Xenotransplantation

The present best approach to enabling xenotransplantation of pig organs into human patients is decellularization: strip all the cells and repopulate the extracellular matrix scaffold of the organ with human cells. However, with the existence of cheap and efficient genetic alteration based on CRISPR it may be possible to edit all of the genes in pig cells that produce problem proteins instead of replacing these cells. My first thought on this is that decellularization is still a better option; after any reasonable number of genetic edits on pig cells the result remains an organ built out of edited pig cells, not human cells, and not matched to the patient. Still, this is an interesting demonstration of the cost-effectiveness of CRISPR, making genetic alterations in much larger batches than have been achieved to date:

For decades, scientists and doctors have dreamed of creating a steady supply of human organs for transplantation by growing them in pigs. But concerns about rejection by the human immune system and infection by viruses embedded in the pig genome have stymied research. By modifying more than 60 genes from pig embryos - ten times more than have been edited in any other animal - researchers believe they may have produced a suitable non-human organ donor.

The researchers used CRISPR gene-editing technology to inactivate 62 porcine endogenous retroviruses (PERVs) in pig embryos. These viruses are embedded in all pigs' genomes and cannot be treated or neutralized. It is feared that they could cause disease in human transplant recipients. They also modified more than 20 genes in a separate set of embryos, including genes encoding proteins that sit on the surface of pig cells and are known to trigger the human immune system or cause blood clotting. Eventually, pigs intended for organ transplants will have both these modifications and the PERV deletions.

A biotech company founded to produce pigs for organ transplantation, eGenesis in Boston, is now trying to make the process as inexpensive as possible. The team released few details about how they managed to remove so many pig genes. But both sets of edited pig embryos are almost ready to implant into mother pigs. eGenesis has procured a facility at Harvard Medical School where the pigs will be implanted and raised in isolation from pathogens.



There is also a possible third approach of growing an organ from human cells inside a humanized pig. Not to sure how far off or feasible this is though.

Posted by: Jim at October 7th, 2015 9:31 AM

Jim, it's probably too slow, I think. Injecting human cells into a pig embryo and waiting for the pig to become adult... maybe the patient is dead by then.

Posted by: Antonio at October 7th, 2015 10:32 AM

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