Progress in multiple genetically modified minipigs for xenotransplantation in China

Area of Science:

• Biotechnology
• Immunology
• Transplantation

Background:

• The critical shortage of human organs necessitates alternatives like xenotransplantation.
• Genetically modified pigs offer anatomical and physiological similarities for organ donation.
• Overcoming immunological rejection and viral transmission are key challenges in xenotransplantation.

Purpose of the Study:

• To review advancements by Chinese scientists in genetically modified pigs for xenotransplantation.
• To highlight strategies for overcoming immunological and viral barriers.
• To present the development of multi-gene low-immunogenicity pigs.

Main Methods:

• Knocking out porcine genes (GGTA1, CMAH, β4GalNT2) to prevent antibody response.
• Inserting human transgenes (CD46, CD55, CD59, hTBM) for immune and coagulation regulation.
• Developing transgenic strategies to mitigate endogenous porcine retrovirus (PERV) risk.

Main Results:

• Successful knockout of key porcine genes reduces antigenicity.
• Human transgenes enhance xenograft compatibility and reduce coagulation issues.
• Strategies to control PERV transmission have been developed.
• Multi-gene low-immunogenicity pigs have been bred in China.

Conclusions:

• Genetic modification of pigs is a viable strategy to address xenotransplantation barriers.
• Chinese scientists have made significant progress in creating suitable pig organ donors.
• Preclinical studies show promise for pig-to-non-human primate xenotransplantation.