PT  - JOURNAL ARTICLE
AU  - Lijin Zou
AU  - Youlai Zhang
AU  - Ying He
AU  - Hui Yu
AU  - Jun Chen
AU  - Delong Liu
AU  - Sixiong Lin
AU  - Manman Gao
AU  - Gang Zhong
AU  - Weicheng Lei
AU  - Guangqian Zhou
AU  - Xuenong Zou
AU  - Kai Li
AU  - Yin Yu
AU  - Gaofeng Zha
AU  - Linxian Li
AU  - Yuanlin Zeng
AU  - Jianfei Wang
AU  - Gang Wang
TI  - Selective germline genome edited pigs and their long immune tolerance in Non Human Primates
AID  - 10.1101/2020.01.20.912105
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.01.20.912105
4099  - http://biorxiv.org/content/early/2020/01/21/2020.01.20.912105.short
4100  - http://biorxiv.org/content/early/2020/01/21/2020.01.20.912105.full
AB  - Organ transplantation is the only curative treatment for patients with terminal organ failure, however, there is a worldwide organ shortage. Genetically modified pig organs and tissues have become an attractive and practical alternative solution for the severe organ shortage, which has been made possible by significant progress in xenotransplantation in recent years. The past several decades witnessed an expanding list of genetically engineered pigs due to technology advancements, however, the necessary combination of genetic modifications in pig for human organ xenotransplantation has not been determined. In the current study, we created a selective germline genome edited pig (SGGEP). The first triple xenoantigens (GGTA, B4GAL, and CAMH) knockout somatic cells were generated to serve as a prototype cells and then human proteins were expressed in the xenoantigen knockout cells, which include human complement system negative regulatory proteins (CD46, CD55, and CD59); human coagulation system negative regulatory proteins thrombomodulin (THBD); tissue factor pathway inhibitor (TFPI); CD39; macrophage negative regulatory proteins (human CD47); and natural killer cell negative regulatory human HLA-E. After the successful establishment of SGGEP by the nuclear tranfer, we engrafted SGGEP skin to NHP, up to 25 days graft survival without immunosuppressive drugs was observed. Because a pig skin graft does not impact the success of a subsequent allograft or autograft or vice versa, thus our SGGEP could have a great potential for clinical value to save severe and large area burn patients and the other human organ failure. Therefore, this combination of specific gene modifications is a major milestone and provides proof of concept to initiate investigator-initiated clinical trials (IITs) in severe burn patients with defined processes and governance measures in place and the other clinical application.