ArticleXenotransplantation2019
Generation of cattle knockout for galactose-α1,3-galactose and N-glycolylneuraminic acid antigens.
Article in Xenotransplantation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 37 citations in OpenAlex.
- Electroporation-mediated site-specific knock-in of a human coding sequence into the bovine ALB locus in embryos.BMC biotechnology · 2026Article
- CRISPR-mediated engineering of bovine satellite cells for Alpha-Gal Syndrome-compatible cultivated meat.bioRxiv : the preprint server for biology · 2026Article
- Ectopic Calcification in Congenital Heart Surgery: A Material-Centric Review.Pediatric cardiology · 2025Review
- Pre-clinical strategies and emerging technologies driving advances in the alpha-gal syndrome.Allergology international : official journal of the Japanese Society of Allergology · 2025Review
- Tissue Preservation and Access: Modern Innovation in Biobanking Moving Forwards a Personalized Treatment.Journal of personalized medicine · 2025Review
- Current Techniques of Gene Editing in Pigs for Xenotransplantation.Transplant international : official journal of the European Society for Organ Transplantation · 2025Review
- Revisiting aortic valve prosthesis choice in patients younger than 50 years: 10 years results of the AUTHEARTVISIT study.European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery · 2024Article
- Differential Immune Response to Bioprosthetic Heart Valve Tissues in the α1,3Galactosyltransferase-Knockout Mouse Model.Bioengineering (Basel, Switzerland) · 2023Article
- Early and midterm outcomes of a bentall operation using an all-biological valved BioConduit™.Journal of cardiothoracic surgery · 2022Article
- Oxidative Stress in Structural Valve Deterioration: A Longitudinal Clinical Study.Biomolecules · 2022Article
- The role of antibody responses against glycans in bioprosthetic heart valve calcification and deterioration.Nature medicine · 2022Article
- Holstein Friesian dairy cattle edited for diluted coat color as a potential adaptation to climate change.BMC genomics · 2021Article
- Article
- Degeneration of Bioprosthetic Heart Valves: Update 2020.Journal of the American Heart Association · 2020Review
- Ultrastructural Pathology of Atherosclerosis, Calcific Aortic Valve Disease, and Bioprosthetic Heart Valve Degeneration: Commonalities and Differences.International journal of molecular sciences · 2020Article
- CRISPR in livestock: From editing to printing.Theriogenology · 2020Review
- Improvements in Gene Editing Technology Boost Its Applications in Livestock.Frontiers in genetics · 2020Review
- Application of a cost-effective DNA extraction protocol for screening transgenic and CRISPR-edited primary goat cells.PloS one · 2020Article
- The Possible Role of Anti-Neu5Gc as an Obstacle in Xenotransplantation.Frontiers in immunology · 2020Review
- Glycosylated Biotherapeutics: Immunological Effects of N-Glycolylneuraminic Acid.Frontiers in immunology · 2020Review
Corrections and comments
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Authors and funding
17 authors at 8 institutions in 4 countries.
Funding
Abstract
Two well-characterized carbohydrate epitopes are absent in humans but present in other mammals. These are galactose-α1,3-galactose (αGal) and N-glycolylneuraminic acid (Neu5Gc) which are introduced by the activities of two enzymes including α(1,3) galactosyltransferase (encoded by the GGTA1 gene) and CMP-Neu5Gc hydroxylase (encoded by the CMAH gene) that are inactive in humans but present in cattle. Hence, bovine-derived products are antigenic in humans who receive bioprosthetic heart valves (BHVs) or those that suffer from red meat syndrome. Using programmable nucleases, we disrupted (knockout, KO) GGTA1 and CMAH genes encoding for the enzymes that catalyse the synthesis of αGal and Neu5Gc, respectively, in both male and female bovine fibroblasts. The KO in clonally selected fibroblasts was detected by polymerase chain reaction (PCR) and confirmed by Sanger sequencing. Selected fibroblasts colonies were used for somatic cell nuclear transfer (SCNT) to produce cloned embryos that were implanted in surrogate recipient heifers. Fifty-three embryos were implanted in 33 recipients heifers; 3 pregnancies were carried to term and delivered 3 live calves. Primary cell cultures were established from the 3 calves and following molecular analyses confirmed the genetic deletions. FACS analysis showed the double-KO phenotype for both antigens confirming the mutated genotypes. Availability of such cattle double-KO model lacking both αGal and Neu5Gc offers a unique opportunity to study the functionality of BHV manufactured with tissues of potentially lower immunogenicity, as well as a possible new clinical approaches to help patients with red meat allergy syndrome due to the presence of these xenoantigens in the diet.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.