Double knockout pigs deficient in N-glycolylneuraminic acid and Galactose α-1,3-Galactose reduce the humoral barrier to xenotransplantation

被引：221

作者：

Lutz, Andrew J. ^{[1
]}

Li, Ping ^{[1
]}

Estrada, Jose L. ^{[1
]}

Sidner, Richard A. ^{[1
]}

Chihara, Ray K. ^{[1
]}

Downey, Susan M. ^{[1
]}

Burlak, Christopher ^{[1
]}

Wang, Zheng-Yu ^{[1
]}

Reyes, Luz M. ^{[1
]}

Ivary, Bess ^{[1
]}

Yin, Fuqin ^{[1
]}

Blankenship, Ross L. ^{[1
]}

Paris, Leela L. ^{[1
]}

Tector, A. Joseph ^{[1
]}

机构：

[1] Indiana Univ Sch Med, Dept Surg, Indianapolis, IN USA

来源：

XENOTRANSPLANTATION | 2013年 / 20卷 / 01期

关键词：

xenotransplantation; Neu5Gc; zinc-finger nuclease; pig; humoral;

D O I：

10.1111/xen.12019

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Background: Clinical xenotransplantation is not possible because humans possess antibodies that recognize antigens on the surface of pig cells. Gal alpha-1,3-Gal (Gal) and N-glycolylneuraminic acid (Neu5Gc) are two known xenoantigens. Methods: We report the homozygous disruption of the alpha 1, 3-galactosyl-transferase (GGTA1) and the cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) genes in liver-derived female pig cells using zinc-finger nucleases (ZFNs). Somatic cell nuclear transfer (SCNT) was used to produce healthy cloned piglets from the genetically modified liver cells. Antibody-binding and antibody-mediated complement-dependent cytotoxicity assays were used to examine the immunoreactivity of pig cells deficient in Neu5Gc and Gal. Results: This approach enabled rapid production of a pig strain deficient in multiple genes without extensive breeding protocols. Immune recognition studies showed that pigs lacking both CMAH and GGTA1 gene activities reduce the humoral barrier to xenotransplantation, further than pigs lacking only GGTA1. Conclusions: This technology will accelerate the development of pigs for xenotransplantation research.

引用

页码：27 / 35

页数：9

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