EBioMedicineJan 4, 2026

Changing sugar molecules through gene editing to reduce immune rejection in modern animal-to-human organ transplants

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

Modern xenotransplantation is being shaped by genome-edited pigs and glycomics tools aimed at reducing glycan-driven graft rejection.

Evidence

This review synthesizes evidence on dominant glycan xenoantigens, multi-gene-edited porcine models, and glycomics-driven epitope discovery for xenotransplantation.

Caveat

Translation remains constrained by limited access to defined glycans and reliable assays for discovering and validating new immunogenic xenoantigens.

Simplified

Xenotransplantation addresses global organ shortages but faces species-specific glycan antigen barriers. Dominant xenoantigens (α-Gal, Neu5Gc, Sda) trigger hyperacute rejection via antibody-mediated immune cascades, complement activation, and thromboinflammation. Advances in precision genome editing, particularly CRISPR-Cas9 now facilitate the generation of multi-gene-edited pigs lacking GGTA1/CMAH/B4GALNT2 to eliminate these epitopes, co-expressing human complement/coagulation regulators to prolong graft survival. The systematic discovery of novel xenoantigens and validation of their immunogenicity, however, are still hampered by limited access to well-defined glycans and reliable functional assays. Emerging technologies, including advanced glycomics, glycoproteomics, and AI-driven prediction, are now accelerating the mapping and prioritisation of immunogenic glycan epitopes. This review synthesises three advances: glycan xenoantigens' immunodominant roles, multi-gene porcine models, and glycomics-driven epitope decoding. These discoveries directly inform next-generation genetic edits and clinical immune monitoring. Convergence of glycobiology, genome engineering, and multi-omics accelerates clinical translation, offering a roadmap for developing rejection-free organs.

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Changing sugar molecules through gene editing to reduce immune rejection in modern animal-to-human organ transplants

Abstract

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