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Double knockout pigs deficient in N ‐glycolylneuraminic acid and G alactose α‐1,3‐ G alactose reduce the humoral barrier to xenotransplantation
Author(s) -
Lutz Andrew J.,
Li Ping,
Estrada Jose L.,
Sidner Richard A.,
Chihara Ray K.,
Downey Susan M.,
Burlak Christopher,
Wang ZhengYu,
Reyes Luz M.,
Ivary Bess,
Yin Fuqin,
Blankenship Ross L.,
Paris Leela L.,
Tector A. Joseph
Publication year - 2013
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1111/xen.12019
Subject(s) - xenotransplantation , somatic cell nuclear transfer , antibody , biology , microbiology and biotechnology , immune system , transplantation , antigen , gene , immunology , biochemistry , medicine , blastocyst , embryogenesis , surgery
Background Clinical xenotransplantation is not possible because humans possess antibodies that recognize antigens on the surface of pig cells. Galα‐1,3‐ G al ( G al) and N ‐glycolylneuraminic acid ( N eu5 G c) are two known xenoantigens. Methods We report the homozygous disruption of the α1, 3‐galactosyltransferase ( GGTA 1) and the cytidine monophosphate‐ N ‐acetylneuraminic acid hydroxylase ( CMAH ) genes in liver‐derived female pig cells using zinc‐finger nucleases ( ZFN s). 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 N eu5 G c and G al. 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 GGTA 1 gene activities reduce the humoral barrier to xenotransplantation, further than pigs lacking only GGTA 1. Conclusions This technology will accelerate the development of pigs for xenotransplantation research.