Double knockout pigs deficient in N-glycolylneuraminic acid and Galactose α-1,3-Galactose reduce the humoral barrier to xenotransplantation
| Autor: | A. Joseph Tector, Leela L. Paris, Christopher Burlak, Bess Ivary, Ping Li, Ray K. Chihara, Luz M. Reyes, R A Sidner, Ross L. Blankenship, Susan M. Downey, Jose L. Estrada, Fuqin Yin, Zheng-Yu Wang, Andrew J. Lutz |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Xenotransplantation
medicine.medical_treatment Sus scrofa Transplantation Heterologous Immunology Antibodies Heterophile Biology Disaccharides Mixed Function Oxygenases Gene Knockout Techniques chemistry.chemical_compound Antigen N-Glycolylneuraminic acid Antigens Heterophile medicine Animals Humans Cytotoxicity Cells Cultured Transplantation Base Sequence Antibody-Dependent Cell Cytotoxicity Cytidine DNA Galactosyltransferases Molecular biology Genetically modified organism chemistry Leukocytes Mononuclear biology.protein Somatic cell nuclear transfer Female Neuraminic Acids Antibody |
| Zdroj: | Xenotransplantation. 20:27-35 |
| ISSN: | 0908-665X |
| DOI: | 10.1111/xen.12019 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|