Medical Breakthrough: Monkey Survives Two Years with Kidney Transplant from Genetically Engineered Pig
Key Highlights :
In a medical breakthrough, researchers at the US biotech company eGenesis and Harvard Medical School have successfully transplanted a kidney from a genetically engineered pig into a monkey, which has survived for more than two years. This experiment may one day develop to be a potential solution to the global shortage of donors for patients with organ failure.
The team of researchers made 69 genomic edits into the pig kidneys to enhance compatibility and reduce rejection by the recipient’s immune system. The donor kidneys carried three types of edits: (1) knock out of three genes involved in the synthesis of glycan antigens implicated in hyperacute rejection, (2) insertion of seven human transgenes involved in the regulation of several pathways that modulate rejection: inflammation, innate immunity, coagulation, and complement, and (3) inactivation of the endogenous retroviruses in the porcine genome.
The results of the experiment showed that donor kidneys carrying human transgenes resulted in longer survival time when transplanted into non-human primates. Donor kidneys containing only knock out of the three-glycan antigens experienced poor graft survival, whereas those harbouring the knockouts and human transgenes resulted in more than seven times longer duration — a median of 24 days versus 176 days, respectively. In the case of one recipient, survival of over two years (758 days) was achieved.
In vitro functional analysis showed that edited porcine kidney endothelial cells modulated inflammation in a manner that mirrored human endothelial cells, suggesting the edited cells acquired a high level of human immune compatibility. Furthermore, the evaluation of renal function biomarkers in recipients with stable grafts revealed that a single transplanted porcine kidney provided sufficient filtration of metabolites to compensate for the lack of two native kidneys.
Organ failure is a life-threatening condition for which transplantation is considered the gold standard treatment. However, the demand for organs far outstrips supply. In addition, the existing organ failure treatment paradigm is suboptimal for patients and the healthcare system due to organ incompatibility and variable donor organ quality.
The successful experiment conducted by researchers at the US biotech company eGenesis and Harvard Medical School, which has resulted in a monkey surviving for more than two years with a kidney transplanted from a genetically engineered pig, is a major step forward in the field of transplantation and may one day provide a potential solution to the global shortage of donors for patients with organ failure.
