ArticleScientific reports2017
Targeted insertion of an anti-CD2 monoclonal antibody transgene into the GGTA1 locus in pigs using FokI-dCas9.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 39 citations in OpenAlex.
- Immunoprotection Strategies in β-Cell Replacement Therapy: A Closer Look at Porcine Islet Xenotransplantation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- Characterisation of transgenic pigs expressing a human T cell-depleting anti-CD2 monoclonal antibody.Xenotransplantation · 2023Article
- Activation of immune signals during organ transplantation.Signal transduction and targeted therapy · 2023Review
- Cardiac xenotransplantation: from concept to clinic.Cardiovascular research · 2023Review
- Progress in xenotransplantation: overcoming immune barriers.Nature reviews. Nephrology · 2022Review
- Advances in CRISPR-Based Functional Genomics and Nucleic Acid Detection in Pigs.Frontiers in genetics · 2022Article
- Cellular Immune Responses in Islet Xenograft Rejection.Frontiers in immunology · 2022Review
- Current status of the application of gene editing in pigs.The Journal of reproduction and development · 2021Review
- CRISPR/Cas Technology in Pig-to-Human Xenotransplantation Research.International journal of molecular sciences · 2021Review
- Review
- Progress towards xenogenic tolerance.Current opinion in organ transplantation · 2020Review
- Xenogeneic cross-circulation for extracorporeal recovery of injured human lungs.Nature medicine · 2020Article
- Improvements in Gene Editing Technology Boost Its Applications in Livestock.Frontiers in genetics · 2020Review
- LIVER TRANSPLANTATION: WILL XENOTRANSPLANTATION BE THE ANSWER TO THE DONOR ORGAN SHORTAGE?Transactions of the American Clinical and Climatological Association · 2020Article
- Transplanting organs from pigs to humans.Science immunology · 2019Review
- Reducing porcine corneal graft rejection, with an emphasis on porcine endogenous retrovirus transmission safety: a review.International journal of ophthalmology · 2019Review
- Xenoantigen Deletion and Chemical Immunosuppression Can Prolong Renal Xenograft Survival.Annals of surgery · 2018Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Xenotransplantation from pigs has been advocated as a solution to the perennial shortage of donated human organs and tissues. CRISPR/Cas9 has facilitated the silencing of genes in donor pigs that contribute to xenograft rejection. However, the generation of modified pigs using second-generation nucleases with much lower off-target mutation rates than Cas9, such as FokI-dCas9, has not been reported. Furthermore, there have been no reports on the use of CRISPR to knock protective transgenes into detrimental porcine genes. In this study, we used FokI-dCas9 with two guide RNAs to integrate a 7.1 kilobase pair transgene into exon 9 of the GGTA1 gene in porcine fetal fibroblasts. The modified cells lacked expression of the αGal xenoantigen, and secreted an anti-CD2 monoclonal antibody encoded by the transgene. PCR and sequencing revealed precise integration of the transgene into one allele of GGTA1, and a small deletion in the second allele. The cells were used for somatic cell nuclear transfer to generate healthy male knock-in piglets, which did not express αGal and which contained anti-CD2 in their serum. We have therefore developed a versatile high-fidelity system for knocking transgenes into the pig genome for xenotransplantation purposes.
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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.