| Literature DB >> 32958897 |
Yanan Yue1, Weihong Xu1, Yinan Kan2, Hong-Ye Zhao3, Yixuan Zhou1, Xiaobin Song1, Jiajia Wu1, Juan Xiong1, Dharmendra Goswami2, Meng Yang1, Lydia Lamriben2, Mengyuan Xu1, Qi Zhang1, Yu Luo1, Jianxiong Guo3, Shengyi Mao3, Deling Jiao3, Tien Dat Nguyen3, Zhuo Li3, Jacob V Layer2, Mailin Li2, Violette Paragas2, Michele E Youd2, Zhongquan Sun4, Yuan Ding4, Weilin Wang4, Hongwei Dou1, Lingling Song1, Xueqiong Wang1, Lei Le1, Xin Fang1, Haydy George2, Ranjith Anand2, Shi Yun Wang2, William F Westlin2, Marc Güell5, James Markmann6, Wenning Qin2, Yangbin Gao1, Hong-Jiang Wei3, George M Church7, Luhan Yang8.
Abstract
The clinical applicability of porcine xenotransplantation-a long-investigated alternative to the scarce availability of human organs for patients with organ failure-is limited by molecular incompatibilities between the immune systems of pigs and humans as well as by the risk of transmitting porcine endogenous retroviruses (PERVs). We recently showed the production of pigs with genomically inactivated PERVs. Here, using a combination of CRISPR-Cas9 and transposon technologies, we show that pigs with all PERVs inactivated can also be genetically engineered to eliminate three xenoantigens and to express nine human transgenes that enhance the pigs' immunological compatibility and blood-coagulation compatibility with humans. The engineered pigs exhibit normal physiology, fertility and germline transmission of the 13 genes and 42 alleles edited. Using in vitro assays, we show that cells from the engineered pigs are resistant to human humoral rejection, cell-mediated damage and pathogenesis associated with dysregulated coagulation. The extensive genome engineering of pigs for greater compatibility with the human immune system may eventually enable safe and effective porcine xenotransplantation.Entities:
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Year: 2020 PMID： 32958897 DOI： 10.1038/s41551-020-00613-9
Source DB: PubMed Journal: Nat Biomed Eng ISSN： 2157-846X Impact factor: 25.671