Cells, tissues, organs, and animals having one or more modified genes for enhanced xenograft survival and tolerance

A method of treating a human subject in need thereof with a genetically modified pig organ, the method comprising:

• providing the genetically modified pig organ to the subject, wherein the genetically modified pig organ comprises a nucleic acid molecule comprising:
• an EPCR transgene, a THBD transgene, an HO1 transgene, a CD46 transgene, a CD55 transgene, and a CD47 transgene;
• wherein the genetically modified pig lacks expression of an alpha-1,3-galactosyltransferase (GGTA1) gene, a β-1,4-N-acetyl-galactosaminyltransferase 2 (4GALNT2) gene, and a cytidine monophosphate-N-acetylneuraminic acid hydrolase (CMAH) gene;
• and
• wherein the CD46 transgene is under the control of a constitutive promoter, whereby the human subject is treated.