Gene Editing Enhances Compatibility of Pig Organs for Human Transplants

Xenotransplantation – the transplantation of animal organs into humans – is a promising solution to the global shortage of organs available for donation.

In 2022, the world’s first pig to human heart transplant occurred at the University of Maryland Medical Center. While the transplant ultimately failed, researchers continue to conduct preclinical experiments using porcine organs and pioneering new methods to optimize their compatibility.

The latest example of such work is led by Dr. Wenning Qin and published in Nature. It describes the design, creation and long-term function of kidney grafts obtained from genetically engineered pigs when transplanted into a nonhuman primate model.

In an interview with Technology Networks, Dr. Wenning Qin discussed why porcine organs are a promising avenue for organ donation, why they can often be rejected and how genome engineering can help increase their compatibility for human transplantation.

Qin and colleagues introduced 69 genome edits into a Yucatan miniature pig, knocking out three glycan antigens believed to induce organ rejection. The researchers also overexpressed seven human transgenes in the pig and inactivated all copies of the gene encoding the porcine retrovirus, reducing the risk of zoonosis.

After transplanting kidney grafts from the pigs to humans, Qin and team found that, when combined with immunosuppressive treatment, the grafts survived for up to 758 days. These results show that preclinical studies of renal xenotransplantation could be successfully conducted in nonhuman primates and bring us closer to clinical trials of genetically engineered porcine renal grafts,” the team writes in Nature. 

Reference: Ranjith P. Anand1,10, Jacob V. Layer1,10, David Heja1,10, Takayuki Hirose2,10, Grace Lassiter2,10, Daniel J. Firl1,2,10, Violette B. Paragas1, , Adam Akkad1, et al. Design and testing of a humanized porcine donor for xenotransplantation. Nature. 2023. doi: 10.1038/s41586-023-06594-4

This article is a rework of a press release issued by Springer Nature. Material has been edited for length and content.