Table 3. Selected genetically-modified pigs currently available for xenotransplantation research.
Complement regulation by human complement-regulatory gene expression |
CD46 (membrane cofactor protein) |
CD55 (decay-accelerating factor) |
CD59 (protectin or membrane inhibitor of reactive lysis) |
Gal or nonGal antigen ‘masking’ or deletion |
Human H-transferase gene expression (expression of blood type O antigen) |
Endo-beta-galactosidase C (reduction of Gal antigen expression) |
α1,3-galactosyltransferase gene-knockout (GTKO) |
Cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) gene-knockout (NeuGcKO) |
β4GalNT2 (β1,4 N-acetylgalactosaminyltransferase) gene-knockout (β4GalNT2KO) |
Human GnT-III (N-acetylglucosaminyltransferase III) gene |
Human tumor necrosis factor-α receptor 1 |
Suppression of cellular immune response by gene expression or downregulation |
CIITA-DN (MHC class II transactivator knockdown, resulting in swine leukocyte antigen class II knockdown) |
Class I MHC-knockout (MHC-IKO) |
HLA-E/human β2-microglobulin (inhibits human natural killer cell and macrophage cytotoxicity) |
Human FAS ligand (CD95L) |
Porcine CTLA4-Ig (Cytotoxic T-Lymphocyte Antigen 4 or CD152) |
Human TRAIL (tumor necrosis factor-alpha-related apoptosis-inducing ligand) |
Anticoagulation and anti-inflammatory gene expression or deletion |
von Willebrand factor (vWF)-deficient (natural mutant) |
Human tissue factor pathway inhibitor (TFPI) |
Human thrombomodulin |
Human endothelial protein C receptor (EPCR) |
Human CD39 (ectonucleoside triphosphate diphosphohydrolase-1) |
Anticoagulation, anti-inflammatory, and anti-apoptotic gene expression |
Human A20 (tumor necrosis factor-alpha-induced protein 3) |
Human heme oxygenase-1 (HO-1) |
Human CD47 (species-specific interaction with SIRP-α inhibits phagocytosis) |
Porcine asialoglycoprotein receptor 1 gene-knockout (ASGR1-KO) (decreases platelet phagocytosis) |
Human signal regulatory protein α (SIRPα) (decreases platelet phagocytosis by ‘self’ recognition) |
Prevention of porcine endogenous retrovirus (PERV) activation |
PERV siRNA |
Based on a table published in J Pathol (Cooper DKC, et al, 2015, in press), courtesy of Burcin Ekser MD, PhD.