One is that our immune system will naturally pick up and reject any of those "xenoantigens" carried by pigs; the other is the risk of pigs passing pathogens like porcine endogenous retroviruses, or PERVs.
AgResearch's Associate Professor Bjorn Oback and his team aimed to genetically remove these xenoantigens from Auckland Island pigs, so their organs could be better matched to human recipients.
The pigs – albeit those that hadn't undergone gene-editing – had already been used to develop successful pig-to-human cell transplants to control diabetes and Parkinson's disease.
These studies had been approved by New Zealand's Medsafe, in consultation with the US Food and Drug Administration and Centers for Disease Control and Prevention.
"Because of their unique birthplace and history, Auckland Island pigs are naturally free from virtually all designated infectious agents," Oback told the Herald.
"Their safety record is due to strict biosecurity measures and the absence of many animal diseases in New Zealand, protecting their high health status."
Housed in designated pathogen-free facilities, these medical-grade pigs were considered the "gold standard" for human biomedical applications, he said.
However, just like other pig breeds, they were still inherently immunogenic.
That's where the latest gene editing approaches might change things.
Oback said his team would draw on CRISPR/Cas9 – a genetic tool often likened to molecular scissors, capable of adding, removing or repairing bits of DNA – to remove those xenoantigens so any transplanted materials would be compatible with humans.
One of his collaborators had recently discovered a novel carbohydrate antigen in Auckland Island pigs, and was now trying to pinpoint its underlying genetic basis.
"Building on this discovery, we hypothesise that eliminating this novel antigen, together with three already known xenoantigens, will create a more favourable cross-match between pig donors and human recipients," he said.
"Pre-clinical validation with antigen-specific assays will evaluate the xenoprotective effect of these measures."
If the study could deliver a proof-of-concept solution, Oback said the potential could be enormous.
"Harnessing New Zealand's geographical isolation, excellent biosecurity systems and high health standard for farm animals, this will expand the unique population of Auckland Island pigs into a national asset with considerable long-term value."
Oback pointed to the severe shortage of transplantable biomaterials facing the world.
Kidneys, in particular, accounted for 66 per cent of all transplants, and more than 80 per cent of patients on waiting lists.
"Importantly, waiting lists fail to capture the true need for organ transplants, which has been estimated at more than 10 times the waiting list," he said.
"In New Zealand, many patients with kidney failure never enter the list or are removed from it by deteriorating health, even death.
"About 2700 people are kept on dialysis instead, even though kidney transplants would greatly improve their life quality and expectancy."
There was also a massive cost involved: the worldwide price of treating end-stage renal disease was estimated to total $1 trillion over a decade.
Last year in New Zealand, there were 589 new cases of end-stage renal disease - with only 183 kidneys transplanted.
"Thus, technologies that can increase the availability of transplant organs are urgently needed."
But it remained to be seen how the public might receive what was a potentially contentious concept, not just because its use of genetic editing, but animals as well.
Beyond those ethical questions, New Zealand heavily regulates such forms of gene editing - namely through the Medicines Act and the Hazardous Substances and New Organisms (HSNO) Act.
A separate programme being led by Oback, and also funded through the Government's Endeavour Fund, involved looking at whether the public would support gene-editing cows to boost milk production and lower their climate change footprint.
