Pig organs have long been considered as a possible option for transplantation into humans, but there is a high risk of rejection. They also pose an infection risk, as fragments of viral DNA known as porcine endogenous retroviruses, or PERVs, are scattered throughout the pig genome. But now, a team of researchers has used CRISPR/Cas9 to remove this DNA to create PERV-free pigs.
'Before our study, there was huge scientific uncertainty about whether the pig [produced after this editing] is viable,' said Dr Luhan Yang co-founder of eGenesis Inc., a company based in Cambridge, Massachusetts, and a lead author on this study. She added: 'We've shown you can produce PERV-free pigs which could serve as a source for future xenotransplants.'
The international team, which includes academic researchers, identified 25 genomic sites at which PERV sequences were present in fetal connective tissue. They then used CRISPR to deactivate these sites. They applied a cocktail of molecules that enabled the PERV-free cells to survive before using a standard cloning method to create embryos. Thirty-seven PERV-free piglets were born, revealed the study published in Science.
Professor Darren Griffin of the University of Kent, who was not involved in the study said: 'This represents a significant step forward towards the possibility of making xenotransplantation a reality. The chance of transmitting PERV from the pig organ to the human cells was a significant barrier and the study shows yet another application of the CRISPR-Cas9 system.'
While calling the study 'very elegant', he added: 'However, there are so many variables including ethical issues to resolve before xenotransplantation can take place.'
Aside from ethical considerations surrounding the future of pig-to-human transplants, technical challenges also remain. The eGenesis team is aiming to deactivate some pig genes and insert others to overcome the risk of rejection.
Dr Yang noted that overcoming the problems with compatibility is 'the second challenge, and probably more challenging [than the PERV research]'.