Why would scientists want to use pigs in organ transplants? What is it about pigs that might make them more suitable as donors as opposed to other animals? What traits might be problematic?
Researchers have focused on using pigs because primate organs carry infectious disease risks, along with ethical concerns. Also, pig organs are a relatively compatible size for humans, and given that we already use pigs for food, there are fewer ethical concerns. Pig tissues and hormones have been used in medicine for years, including for heart valves, insulin, and hormones.
Why would we need to edit pigs’ genes for this to work? What are scientists looking to remove or change when they edit a pig’s gene with CRISPR?
Since pigs are further down the evolutionary tree than primates, their organs express many different proteins and sugars than human organs. Some of these differences elicit strong immune responses in recipients, and others prevent the organs from interacting perfectly with human blood. Our group at NewYork-Presbyterian/Columbia and other researchers have been focused on eliminating harmful proteins or sugars and adding essential human proteins to the pig. This recent research used CRISPR, a genome-editing tool, to remove the traces of a pig retrovirus, with the aim of reducing the risk that organ recipients would develop a viral infection after transplant.
Why is this recent paper such a potential breakthrough for xenotransplantation?
Altering the genetics of the pig has become much easier and quicker using CRISPR. The production of a living pig from this altered genome is still a hurdle. In this report, the researchers describe that they have generated viable pigs after CRISPR removed the porcine endogenous retrovirus (commonly called “PERV”) genes. Therefore, it represents a step forward in making xenotransplantation less theoretically risky from an infectious disease perspective.
What are the next steps in terms of pushing this science forward?
For xenotransplantation to be practical for patients, researchers still need to figure out how to perform modifications to “humanize” the pig organs, at least in terms of the organs’ interaction with human blood and the human immune system.
When do you expect doctors will use pig organs in humans?
For select patients, pig organs or cells such as islets may be a reasonable option in the next few years. There are many groups in the U.S. and the world that have been working on the necessary genetic additions or subtractions to enable the organs to function normally after transplantation. With continued support, this line of research holds great promise.