ArticleScientific reports2016
Efficient production of multi-modified pigs for xenotransplantation by 'combineering', gene stacking and gene editing.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 157 citations in OpenAlex.
- Diminished immune cell adhesion in hypoimmune ICAM-1 knockout human pluripotent stem cells.Nature communications · 2025Article
- Assessing the Function of Porcine A Kinase-Interacting Protein 1 (AKIP1) In Vitro-A Central Regulator of Oxidative Stress and Mitochondrial Functions.International journal of molecular sciences · 2025Article
- Perinatal death in pig models of hypertrophic cardiomyopathy carrying sarcomere pathogenic variants.Journal of molecular and cellular cardiology plus · 2025Article
- Comparison Between Electroporation at Different Voltage Levels and Microinjection to Generate Porcine Embryos with Multiple Xenoantigen Knock-Outs.International journal of molecular sciences · 2024Article
- Engineering immune-evasive allogeneic cellular immunotherapies.Nature reviews. Immunology · 2024Review
- Genetic engineering drives the breakthrough of pig models in liver disease research.Liver research (Beijing, China) · 2024Review
- Gene-edited pigs: a translational model for human food allergy against alpha-Gal and anaphylaxis.Frontiers in immunology · 2024Article
- Genetic Engineering of Donor Pig for the First Human Cardiac Xenotransplantation: Combatting Rejection, Coagulopathy, Inflammation, and Excessive Growth.Current cardiology reports · 2023Review
- Comparative transcriptome analysis between long- and short-term survival after pig-to-monkey cardiac xenotransplantation reveals differential heart failure development.Animal cells and systems · 2023Article
- How genome editing changed the world of large animal research.Frontiers in genome editing · 2023Review
- Transgenesis and Genome Engineering: A Historical Review.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Towards human organ generation using interspecies blastocyst complementation: Challenges and perspectives for therapy.Frontiers in cell and developmental biology · 2023Review
- Progress in xenotransplantation: overcoming immune barriers.Nature reviews. Nephrology · 2022Review
- Strategies for Expanding Donors Pool in Heart Transplantation.Reviews in cardiovascular medicine · 2022Review
- Xenotransplantation becoming reality.Transgenic research · 2022Review
- Progressive genetic modifications of porcine cardiac xenografts extend survival to 9 months.Xenotransplantation · 2022Article
- Potentials, prospects and applications of genome editing technologies in livestock production.Saudi journal of biological sciences · 2022Review
- Advances in pig models of human diseases.Animal models and experimental medicine · 2022Review
- The future treatment for type 1 diabetes: Pig islet- or stem cell-derived β cells?Frontiers in endocrinology · 2022Review
- Blastocyst complementation and interspecies chimeras in gene edited pigs.Frontiers in cell and developmental biology · 2022Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
22 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Xenotransplantation from pigs could alleviate the shortage of human tissues and organs for transplantation. Means have been identified to overcome hyperacute rejection and acute vascular rejection mechanisms mounted by the recipient. The challenge is to combine multiple genetic modifications to enable normal animal breeding and meet the demand for transplants. We used two methods to colocate xenoprotective transgenes at one locus, sequential targeted transgene placement - 'gene stacking', and cointegration of multiple engineered large vectors - 'combineering', to generate pigs carrying modifications considered necessary to inhibit short to mid-term xenograft rejection. Pigs were generated by serial nuclear transfer and analysed at intermediate stages. Human complement inhibitors CD46, CD55 and CD59 were abundantly expressed in all tissues examined, human HO1 and human A20 were widely expressed. ZFN or CRISPR/Cas9 mediated homozygous GGTA1 and CMAH knockout abolished α-Gal and Neu5Gc epitopes. Cells from multi-transgenic piglets showed complete protection against human complement-mediated lysis, even before GGTA1 knockout. Blockade of endothelial activation reduced TNFα-induced E-selectin expression, IFNγ-induced MHC class-II upregulation and TNFα/cycloheximide caspase induction. Microbial analysis found no PERV-C, PCMV or 13 other infectious agents. These animals are a major advance towards clinical porcine xenotransplantation and demonstrate that livestock engineering has come of age.
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