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Porcine genome engineering for xenotransplantation

文献类型: 外文期刊

作者: Niu, Dong 1 ; Ma, Xiang 1 ; Yuan, Taoyan 6 ; Niu, Yifan 4 ; Xu, Yibin 8 ; Sun, Zhongxin 5 ; Ping, Yuan 9 ; Li, Weifen 8 ; Zh 1 ;

作者机构: 1.Zhejiang A&F Univ, Key Lab Appl Technol Green Ecohlthy Anim Husb Zhe, China Australian Joint Lab Anim Hlth Big Data An, Coll Anim Sci & Technol,Zhejiang Prov Engn Lab An, Hangzhou, Peoples R China

2.Zhejiang A&F Univ, Coll Vet Med, Hangzhou, Peoples R China

3.Harvard Med Sch, Dept Genet, 77 Ave Louis Pasteur, Boston, MA 02115 USA

4.Nanjing Kgene Genet Engn Co Ltd, Nanjing 211300, Jiangsu, Peoples R China

5.Hangzhou First Peoples Hosp, Cosmet & Plast Surg Dept, Hangzhou 310006, Zhejiang, Peoples R China

6.Zhejiang Acad Agr Sci, Inst Anim Husb & Vet Sci, Hangzhou 310021, Zhejiang, Peoples R China

7.Harvard Univ, Wyss Inst Biol Inspired Engn, Cambridge, MA 02138 USA

8.Zhejiang Univ, Coll Anim Sci, Hangzhou 310058, Zhejiang, Peoples R China

9.Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou 310058, Zhejiang, Peoples R China

关键词: Xenotransplantation; Pig; Immune rejection; Inflammation; Coagulation; Porcine endogenous retrovirus (PERV); Genetic modification; Preclinical trials

期刊名称:ADVANCED DRUG DELIVERY REVIEWS ( 影响因子:15.47; 五年影响因子:18.881 )

ISSN: 0169-409X

年卷期: 2021 年 168 卷

页码:

收录情况: SCI

摘要: The extreme shortage of human donor organs for treatment of patients with end-stage organ failures is well known. Xenotransplantation, which might provide unlimited organ supply, is a most promising strategy to solve this problem. Domestic pigs are regarded as ideal organ-source animals owing to similarity in anatomy, physiology and organ size to humans as well as high reproductive capacity and low maintenance cost. However, several barriers, which include immune rejection, inflammation and coagulative dysfunctions, as well as the cross-species transmission risk of porcine endogenous retrovirus, blocked the pig-tohuman xenotransplantation. With the rapid development of genome engineering technologies and the potent immunosuppressive medications in recent years, these barriers could be eliminated through genetic modification of pig genome together with the administration of effective immunosuppressants. A number of candidate genes involved in the regulation of immune response, inflammation and coagulation have been explored to optimize porcine xenograft survival in non-human primate recipients. PERV inactivation in pigs has also been accomplished to firmly address the safety issue in pig-to-human xenotransplantation. Many encouraging preclinical milestones have been achieved with some organs surviving for years. Therefore, the clinical trials of some promising organs, such as islet, kidney and heart, are aimed to be launched in the near future. (c) 2020 Published by Elsevier B.V.

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