| 1. Pig gene knockouts to prevent hyperacute rejection from human antibodies to pig sugars |
| a. α-1-3 galactosyltransferase—enzyme responsible for synthesis of galactose-α-1-3-galactose (α-1-3GAL) |
| b. β-1,4-N-acetylgalactosyltransferease—enzyme responsible for synthesis of non-GAL polysaccharide DBA-reactive glycan (also known as Sda antigen) |
| c. CMP-N-acetylneuraminic acid hydroxylase—enzyme responsible for synthesis of Neu5Sc |
| 2. Pig gene knockout to prevent excessive growth of pig kidney |
| a. Porcine growth hormone receptor gene |
| 3. Insertions of human genes into pig genome |
| a. Human compliment inhibitor genes |
| i. hDAF—decay accelerating factor, membrane protein that inhibits activation of compliment C3 component |
| ii. hCD46—membrane cofactor protein responsible for regulating human compliment cascade |
| b. Human anti-coagulant genes |
| i. hTBM—human thrombomodulin on pig endothelial cells to inhibit prothrombinase and delay clotting |
| ii. hEPCR—endothelial protein C receptor to reduce thrombin generation and platelet aggregation |
| c. Human immunomodulatory genes |
| i. hCD47—integrin transmembrane protein to prevent phagocytosis (‘don't eat me’ protein) |
| ii. hHO1—heme oxygenase 1 antioxidant enzyme that reduces inflammation and prevents apoptosis |
