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Published on: January 6, 2022
Porcine genome engineering for xenotransplantation
Dong Niu1, Xiang Ma1, Taoyan Yuan2
1Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, China-Australian Joint Laboratory for Animal Health Big Data Analytics, Zhejiang Provincial Engineering Laboratory for Animal Health Inspection & Internet Technology, College of Animal Science and Technology & College of Veterinary Medicine of Zhejiang A&F University, Hangzhou, P.R. China.
Xenotransplantation using genetically modified pigs offers a promising solution to the organ shortage. Overcoming immune rejection and viral risks paves the way for clinical trials of pig organs in humans.
Area of Science:
- Transplantation immunology
- Genomics
- Veterinary medicine
Background:
- Severe shortage of human donor organs for end-stage organ failure patients.
- Xenotransplantation, particularly from domestic pigs, is a promising solution due to physiological similarities and organ availability.
- Significant barriers include immune rejection, inflammation, coagulation issues, and porcine endogenous retrovirus (PERV) transmission.
Purpose of the Study:
- To address the barriers hindering pig-to-human xenotransplantation.
- To optimize porcine xenografts for survival in non-human primate models.
- To ensure the safety of xenotransplantation by inactivating PERV.
Main Methods:
- Genetic modification of pig genomes to mitigate immune responses, inflammation, and coagulation disorders.
- Administration of potent immunosuppressive medications.
- Inactivation of porcine endogenous retrovirus (PERV) in donor pigs.
Main Results:
- Successful genetic modifications and immunosuppression strategies have been developed.
- Preclinical studies show encouraging xenograft survival, with some organs functioning for years in non-human primates.
- PERV inactivation has been achieved, addressing cross-species transmission risks.
Conclusions:
- Genetic engineering and immunosuppression have overcome major xenotransplantation barriers.
- Preclinical success indicates readiness for clinical translation.
- Clinical trials for pig islets, kidneys, and hearts are anticipated soon.
