Xenotransplantation (cross-species transplantation) is discussed in Box 14.2 of Principles of Gene Manipulation (p 287). For a number of reasons, pigs are considered particularly suitable donors for organ transplants to humans (see Sandrin & McKenzie 1999, Logan 2000). However, the major obstacle in pig-to-human organ transplantation is the phenomenon of hyperacute rejection, caused primarily by the response of the human immune system to a specific disaccharide group - Gal -α(1,3)-Gal - present on pig but not primate cells. Transgenic technology could be used to avoid hyperacute rejection and we note in the text of Box 14.2 that a simple strategy would be to knock out the gene, encoding the enzyme α-1,3-galactosyltransferase, responsible for forming that carbohydrate linkage.

Early in 2002, two groups reported that they had achieved this goal (Dai et al. 2002, Lai et al. 2002). In both cases, several live piglets were born following nuclear transfer, from foetal fibroblasts in which the α-1,3-galactosyltransferase gene had been disrupted by gene targeting with a homologous construct, to enucleated oocytes. Dai and colleagues, from PPL Therapeutics, reported the birth of five healthy piglets on Christmas Day 2001 (these were appropriately named Noel, Angel, Star, Joy and Mary). Lai and colleagues, from the University of Missouri-Colombia and Immerge BioTherapeutics Inc., claim their four piglets were born about three months earlier. The pigs used by Lai and colleagues were of a miniature breed, which may have advantages, in terms of organ size, for human recipients.

References:

Dai Y, Vaught TD, Boone J, Chen S-H et al. (2002) Targeted disruption of the Α-1,3-galactosyltransferase gene in cloned pigs. Nature Biotechnol 20, 251-5.

Lai L, Kolber-Simonds D, Park K-W, Cheong H-T et al. (2002) Production of Α-1,3-galactosyltransferase knockout pigs by nuclear transfer cloning. Science 295, 1089-92.

Logan JS (2000) Prospects for xenotransplantation. Curr Opin Immunol 12, 563-8.

Sandrin MS, McKenzie IFC (1999) Recent advances in xenotransplantation. Curr Opin Immunol 11, 527-31.