Table 4.

Immunological target genes for a gene-editing in pig xenotransplants.

Rejection period	Immune response	Rejection mechanism	Target gene editing
Hyperacute	Innate	Reduction of natural anti- αGal responses by deleting αGal epitope	•α-1,3 galactosyltransferase knockout (GT-KO) •human H-transferase expression
Acute	Innate	Complement regulation	•human CD59 expression •human CD55 expression •human CD46 expression
		Coagulation/thrombosis reduction	•human thrombomodulin expression •human tissue factor pathway inhibitor expression •human CD39 expression
		Natural Killer cells regulation	•human leukocyte antigen G (HLA-G), HLA-E expression •human beta2 microglobulin expression
		Macrophage/monocyte regulation	•human CD47 expression (a marker for “self”) •human signal regulatory protein alpha expression •human heme oxygenase 1 expression •human A20 expression •human CD39 expression
Chronic	Adaptive	T cells	•MHC II transactivator dominant negative knockout •MHC class I knockout •Cytotoxic T lymphocyte antigen 4-IgG Fc expression
		B cells	•GT-KO •CMP-N-acetylneuraminic hydroxylase knockout

AbbreviationsαGal: Galα1-3Galβ1-4GlcNAc-R, MHC: major histocompatibility complex.