Xenotransplantation

Technological Innovations

We use the gene editing technology tools including zinc finger nuclease (ZFN), Tal effector endogenous nuclease (TALEN), and CRISPR/Cas9 to produce our transgenic pigs. We use also homologous recombination technology for precise genetic engineering such as the knock-in of the transgene. We developed 7 transgenic pigs with the knock-out of the α-gal inducing hyperacute rejection, which is a severe immunological rejection following xenotransplantation, and knock-in of the human CD46 (a membrane cofactor protein) or human CD55 (a decay-accelerating factor) to modulate complement-mediated immunological rejection effects.

Somatic Cell Nuclear Transfer (SCNT) and Cloning

Somatic cell nuclear transfer (SCNT) consists of the removal of the nucleus from recipient oocytes and replacement the nucleus with somatic cells to produce a cloned animal, and is a key technology required for xenotransplantation resource production. A genetically modified pig can be produced by inserting somatic cells with genetic manipulation to control immune rejection to enucleated oocytes, then planting the cloned embryos into the surrogate sow.

Breeding of Transgenic Pigs

Optipharm has the rights and licenses to Yucatan minipigs from Sinclair Research in the US, and the animals for xenotransplantation is managed in designated pathogen free (DPF) facilities with the highest level of hygiene standards recommended by the International xenotransplantation Association (IXA). In addition, cesarean-derived colostrum-deprived (CDCD) pig production technology is used to prevent the transfer of maternal antibodies to piglets during birth. Transgenic pigs based on blood type O and is PERV-C negative in order to suppress the immune response in xenotransplantation that have reached sexual maturation are bred both naturally and through artificial insemination to produce herds by genetic type clusters or other transgenic pigs with new genotypes. For efficient reproduction, we utilize various breeding technologies such as selection of the pig through reproduction capability examination of the boar and using genogram analysis.

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