Cited by 294Xenotransplantation and immune responseAnimal Genetics and ReproductionGlycosylation and Glycoproteins Research

The DOI matches its Crossref record; 16 of the 16 references it cites were found in a registry or an index.

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

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Abstract

BACKGROUND: 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. METHODS: 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. 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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Crossref · 10.1111/xen.12019

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  1. Li P, 2012, Biallelic knockout of the alpha‐1,3 galactosyltransferase gene in porcine liver‐derived cells using zinc finger nucleases, J Surg Res

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Metadata

Authors
Lutz, A. J., Li, P., Estrada, J. L., Sidner, R. A., Chihara, R. K., Downey, S. M., Burlak, C., Wang, Z., Reyes, L. M., Ivary, B., Yin, F., Blankenship, R. L., Paris, L. L., & Tector, A. J.
Affiliations
Indiana University Indianapolis (US)
Corresponding author
Tector, A. Joseph
Venue
Xenotransplantation
Publisher
Wiley
Published
2013-01
Volume
20
Issue
1
Pages
27-35
ISSN
  • 0908-665X (ISSN-L)
  • 1399-3089
OpenAlex
W1979411388
Cited by
294
References
16
Citations by year
2026: 11 · 2025: 16 · 2024: 18 · 2023: 19 · 2022: 17 · 2021: 10 · 2020: 24 · 2019: 29 · 2018: 16 · 2017: 22 · 2016: 33 · 2015: 32 · 2014: 31 · 2013: 15
FWCI
36.44
Type
journal article
Language
en
Open access
Locations
  • Xenotransplantation (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Langley Research Center
  • National Center for Research Resources (C06RR010601, C06RR10601-01)
Topics
  • Health Sciences › Medicine › Surgery › Xenotransplantation and immune response
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Animal Genetics and Reproduction
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
Keywords
N-glycolylneuraminic acid, galactose-alpha-1,3-galactose, xenoantigens, GGTA1, CMAH, knockout pigs, somatic cell nuclear transfer, zinc finger nucleases, humoral immune response, genetically modified pigs
MeSH terms
Animals, Antibodies, Heterophile, Antibody-Dependent Cell Cytotoxicity, Base Sequence, Cells, Cultured, Disaccharides, DNA, Female, Galactosyltransferases, Humans, Mixed Function Oxygenases, Leukocytes, Mononuclear, Neuraminic Acids, Transplantation, Heterologous, Antigens, Heterophile, Sus scrofa, Gene Knockout Techniques

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