Table 1. Genetically-modified pigs currently available for xenotransplantation research*.
Pig model | Modified genes |
Gal antigen deletion or ‘masking’ | α1,3-galactosyltransferase gene-knockout (GTKO) |
Human H-transferase gene expression (expression of blood type O antigen) | |
Endo-beta-galactosidase C (reduction of Gal antigen expression) | |
NonGal antigen deletion | N-glycolylneuraminic acid (NeuGc-KO) + α1,3-galactosyltransferase gene-knockout (GTKO) |
Complement regulation by human complement-regulatory gene expression | CD46 (membrane cofactor protein) |
CD55 (decay-accelerating factor) | |
CD59 (protectin or membrane inhibitor of reactive lysis) | |
Anticoagulation and anti-inflammatory gene expression or deletion | Human tissue factor pathway inhibitor (TFPI) |
Human thrombomodulin | |
Human CD39 (ectonucleoside triphosphate diphosphohydrolase-1) | |
Von Willebrand factor (vWF)-deficient (natural mutant) | |
Human endothelial protein C receptor (EPCR) | |
Suppression of cellular immune response by gene expression or downregulation | Porcine CTLA4-Ig (Cytotoxic T-Lymphocyte Antigen 4 or CD152) |
LEA29Y (Inhibition of the B7/CD28 co-stimulatory pathway of T-cell activation) | |
CIITA-DN (MHC class II transactivator knockdown, resulting in swine leukocyte antigen class II knockdown) | |
Human TRAIL (tumor necrosis factor-alpha-related apoptosis-inducing ligand) | |
HLA-E/human β2-microglobulin (inhibits human natural killer cell cytotoxicity) | |
Human CD47 (for species-specific CD47-SIRPalpha natural interaction on macrophages) | |
Human FAS ligand (CD95L) | |
Human GnT-III (N-acetylglucosaminyltransferase III) gene | |
Anticoagulation, anti-inflammatory, and anti-apoptotic gene expression | Human A20 (tumor necrosis factor-alpha-induced protein 3) |
Human heme oxygenase-1 (HO-1) | |
Human TNFRI-Fc (tumor necrosis factor-alpha receptor I-Fc) | |
Prevention of porcine endogenous retrovirus (PERV) activation | PERV siRNA |
* Modified from Cooper DKC, et al.[10]
Pigs with combinations of genetic modification, e.g., GTKO with added transgenes, are available.