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
Open accessAbstract
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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“However, regulatory issues, complexity, time-consuming process, and high costs are among the main barriers that need to be addressed in these methods [133, 185].”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [133]
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“Xenogeneic sialic acids are one of the leading non-α-gal antigens, participating in the rejection of xenografts [133–135].”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [133]
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“Exposing cells of GT-CMAH knockout pigs (which lack expression of α-gal and Neu5Gc epitopes) to human serum demonstrates fewer antigen-antibody reactions [133, 134].”
From Immunogenicity of decellularized extracellular matrix scaffolds: a bottleneck in tissue engineering and regenerative medicine (2023) · cites this paper as [133]
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“glycans like ɑ -Gal and the nonhuman sialic acid Neu5Gc represent the major xenoantigens that must be bypassed, to pursue the goal of xeno- (pig organ) transplantation into humans. In pursuit of this dif fi cult goal, ɑ -Galand Neu5Gc-double null pigs have recently been generated (980 -983).”
From Biological roles of glycans (2017) · cites this paper as [980]
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Production of α1,3-Galactosyltransferase-Deficient Pigs
Phelps, C. J., Koike, C., Vaught, T. D., Boone, J. T., Wells, K. D., Chen, S.-H., Ball, S. F., Specht, S. M., Polejaeva, I. A., Monahan, J. A., et al. (2003) · Science · doi:10.1126/science.1078942 · Cited by 1,111
Targeted disruption of the α1,3-galactosyltransferase gene in cloned pigs
Dai, Y., Vaught, T. D., Boone, J. T., Chen, S.-H., Phelps, C. J., Ball, S. F., Monahan, J. A., Jobst, P. M., McCreath, K. J., Lamborn, A. E., et al. (2002) · Nature Biotechnology · doi:10.1038/nbt0302-251 · Cited by 713
Kolber, D. L., Lai, L., Watt, S. R., Denaro, M., Arn, S., Augenstein, M. L., Betthauser, J. M., Carter, D. B., Greenstein, J. L., Hao, Y., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0307819101 · Cited by 458
Efficient generation of a biallelic knockout in pigs using zinc-finger nucleases
Hauschild‐Quintern, J., Petersen, B., Santiago, Y., Queisser, A. L., Carnwath, J. W., Lucas‐Hahn, A., Zhang, L., Meng, X., Gregory, P. D., Schwinzer, R., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1106422108 · Cited by 370
Chen, G., Qian, H., Starzl, T. E., Sun, H., Garcia, B. M., Wang, X., Wise, Y., Liu, Y., Xiang, Y., Copeman, L. S., et al. (2005) · Nature Medicine · doi:10.1038/nm1330 · Cited by 357
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Functionally important glycosyltransferase gain and loss during catarrhine primate emergence
Koike, C., Uddin, M., Wildman, D. E., Gray, E. A., Trucco, M., Starzl, T. E., & Goodman, M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610012104 · Cited by 84
Complement regulation in the GalT KO era
Miyagawa, S., Yamamoto, A., Matsunami, K., Wang, D., Takama, Y., Ueno, T., Okabe, M., Nagashima, H., & Fukuzawa, M. (2010) · Xenotransplantation · doi:10.1111/j.1399-3089.2010.00569.x · Cited by 73
Song, K., Kang, Y., Jin, U., Park, Y. I., Kim, S., Seong, H., Hwang, S., Yang, B.-S., Im, G., Min, K., et al. (2010) · Biochemical Journal · doi:10.1042/bj20090835 · Cited by 62
Human-specific evolution of sialic acid targets: Explaining the malignant malaria mystery?
Varki, A., & Gagneux, P. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0908196106 · Cited by 62
Basnet, N. B., Ide, K., Tahara, H., Tanaka, Y., & Ohdan, H. (2010) · Xenotransplantation · doi:10.1111/j.1399-3089.2010.00610.x · Cited by 45
Genetic engineering including superseding microinjection: new ways to make GM pigs
Galli, C., Perota, A., Brunetti, D., Lagutina, I., Lazzari, G., & Lucchini, F. (2010) · Xenotransplantation · doi:10.1111/j.1399-3089.2010.00590.x · Cited by 33
Whyte, J. J., & Prather, R. S. (2011) · Journal of Animal Science · doi:10.2527/jas.2011-4546 · Cited by 30
Gene Targeting and Cloning in Pigs Using Fetal Liver Derived Cells
Waghmare, S. K., Estrada, J. L., Reyes, L. M., Li, P., Ivary, B., Sidner, R. A., Burlak, C., & Tector, A. J. (2011) · Journal of Surgical Research · doi:10.1016/j.jss.2011.07.051 · Cited by 20
Self-citationDiaz, T., Moscoso, I., Centeno, A., López-Peláez, E., Ortega, D., & Doménech, N. (2004) · Transplant Immunology · doi:10.1016/j.trim.2004.09.001 · Cited by 15
Li, P., Estrada, J. L., Zhang, F., Waghmare, S. K., & Mir, B. (2010) · Cellular Reprogramming · doi:10.1089/cell.2010.0006 · Cited by 11
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Research works printed but not linked: 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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Varki, A. (2017) · Glycobiology · doi:10.1093/glycob/cww086 · Cited by 2,635
Glycosylation in health and disease
Reily, C., Stewart, T. J., Renfrow, M. B., & Novak, J. (2019) · Nature Reviews Nephrology · doi:10.1038/s41581-019-0129-4 · Cited by 2,075
Estrada, J. L., Martens, G., Li, P., Adams, A., Newell, K. A., Ford, M. L., Butler, J. R., Sidner, R., Tector, M., & Tector, J. (2015) · Xenotransplantation · doi:10.1111/xen.12161 · Cited by 417
Self-citationKasravi, M., Ahmadi, A., Babajani, A., Mazloomnejad, R., Hatamnejad, M. R., Shariatzadeh, S., Bahrami, S., & Niknejad, H. (2023) · Biomaterials Research · doi:10.1186/s40824-023-00348-z · Cited by 316
Long-term survival of pig-to-rhesus macaque renal xenografts is dependent on CD4 T cell depletion
Kim, S. C., Mathews, D. V., Breeden, C. P., Higginbotham, L. B., Ladowski, J., Martens, G., Stephenson, A., Farris, A. B., Strobert, E. A., Jenkins, J., et al. (2019) · American Journal of Transplantation · doi:10.1111/ajt.15329 · Cited by 232
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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
- ORCID
- 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
- bronze
- doi.org
- 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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