期刊
XENOTRANSPLANTATION
卷 20, 期 1, 页码 27-35出版社
WILEY-BLACKWELL
DOI: 10.1111/xen.12019
关键词
xenotransplantation; Neu5Gc; zinc-finger nuclease; pig; humoral
资金
- IU Health Transplant Institute
- National Center for Research Resources, National Institute of Health [C06RR10601-01]
- NATIONAL CENTER FOR RESEARCH RESOURCES [C06RR010601] Funding Source: NIH RePORTER
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.
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