There is a massive shortage of transplant organs worldwide, and scientists are desperate to come up with a solution — whether that be boosting patient’s immune systems to let them accept otherwise incompatible organs, or creating technology for preserving organs after they are harvested. A new international research initiative has another approach: Using CRISPR gene editing on pigs to make them into safe organ donor candidates for humans.
The reason pigs are desirable as possible sources of organs is that their organs are similar to humans in both size and anatomy. Unfortunately, they also carry viruses — known as porcine endogenous retroviruses (PERVs) — embedded in their DNA. As this research demonstrated, this can be passed on to humans, although gene editing can be used to eradicate it.
“Currently, the major problem of human transplants is the great shortage of transplantable human organs,” Lin Lin, a researcher in the department of biomedicine at Denmark’s Aarhus University, told Digital Trends. “While using pig organs, we can in principle use as many as we need. Eradicating PERVs makes porcine organs safer for human transplants. However, there are still several other barriers that we have to cross in order to make pig organs better for human transplants. This is now achievable with the great development in CRISPR gene editing.”
Using an optimized CRISPR-Cas9 gene editing technology and porcine somatic cell nuclear transfer, this work successfully generated viable pigs that are 100 percent PERV-inactivated. Thirty-seven PERV-inactive piglets have so far been born, with 15 remaining alive. The oldest of these is four months old, which means it will need to be monitored for a longer period of time to make sure it suffers no ill-effects.
“The next major step is to solve the problem of vigorous immune responses, such as complement activation, coagulation and thrombosis, triggered by xenotransplantation,” Lin said. “Many previous works have demonstrated that the immunological incapability can be alleviated through tailoring the pig genome. Thus, a serial of very sophisticated gene editing and modifications will be further introduced into the PERV-inactivated pigs and tested in higher primates.”
A paper describing the research was recently published in the journal Science.