Glycoprotein alpha-1,3-galactosyltransferase 1 (GGTA1) (GGTA1)

The porcine GGTA1 gene encodes the enzyme alpha-1,3-galactosyltransferase, which is responsible for synthesizing the alpha-gal (Gal-alpha-1,3-Gal) carbohydrate epitope on cell surfaces [1, 2]. While this enzyme is present in most mammals, it is functionally absent in humans and Old World primates due to the evolutionary inactivation of the GGTA1 gene [3, 4]. Consequently, humans possess high levels of natural pre-formed antibodies against the alpha-gal epitope, which trigger hyperacute rejection of porcine organ xenografts within minutes of transplantation [3, 5]. To overcome this immunological barrier, the GGTA1 gene is the primary target for genetic engineering in pigs intended for xenotransplantation, typically through gene knockout techniques using CRISPR-Cas9 or other site-specific nucleases [5, 6]. Eliminating GGTA1 expression significantly reduces the immediate immune response, making it a foundational modification for the development of pigs as viable organ donors for human patients [3, 6]. Beyond its role in transplantation, the alpha-gal epitope is also the causative agent in alpha-gal syndrome, a delayed allergic reaction to red meat induced by tick bites [4]. [1] UniProt (P50127); [2] NCBI Gene (ID: 397434); [3] Cooper DKC, et al. (2002) PMID: 12069613; [4] Galili U. (2005) PMID: 15849282; [5] Lu T, et al. (2013) PMID: 23653343; [6] Perota A, et al. (2016) PMID: 27113123.

Other names

Alpha-1,3-galactosyltransferaseAlpha1,3GTN-acetyllactosaminide alpha-1,3-galactosyltransferaseGalactosyltransferase induced by GALUDP-Gal:beta-D-Gal(1,4)-D-GlcNAc alpha(1,3)-galactosyltransferase

Targeted genomic disruption (knockout) to eliminate the expression of the alpha-1,3-galactosyltransferase enzyme, thereby preventing the synthesis of alpha-gal epitopes on the cell surface to avoid antibody-mediated rejection.