Both authors contributed equally to this work.
Double knockout pigs deficient in N-glycolylneuraminic acid and Galactose α-1,3-Galactose reduce the humoral barrier to xenotransplantation
Article first published online: 5 FEB 2013
© 2013 John Wiley & Sons A/S
Volume 20, Issue 1, pages 27–35, January/February 2013
How to Cite
Double knockout pigs deficient in N-glycolylneuraminic acid and Galactose α-1,3-Galactose reduce the humoral barrier to xenotransplantation. Xenotransplantation 2013; 20: 27–35. © 2013 John Wiley & Sons A/S., , , , , , , , , , , , , .
- Issue published online: 5 FEB 2013
- Article first published online: 5 FEB 2013
- Manuscript Accepted: 20 DEC 2012
- Manuscript Received: 1 OCT 2012
- zinc-finger nuclease;
Clinical xenotransplantation is not possible because humans possess antibodies that recognize antigens on the surface of pig cells. Galα-1,3-Gal (Gal) and N-glycolylneuraminic acid (Neu5Gc) are two known xenoantigens.
We report the homozygous disruption of the α1, 3-galactosyltransferase (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.
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.
This technology will accelerate the development of pigs for xenotransplantation research.