ArticleJCI insight2020
A porcine model of phenylketonuria generated by CRISPR/Cas9 genome editing.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The trial behind it
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Who cites it
19 citing papers in PubMed, 43 citations in OpenAlex.
- Global Trends in Phenylketonuria Treatment Research, 2000-2025: Bibliometric Analysis.Online journal of public health informatics · 2026Article
- Enhancing the specificity of gene editing outcomes by using Cas9 variants in porcine embryos.Journal of animal science · 2026Article
- Advancing Gene Therapy for Phenylketonuria: From Precision Editing to Clinical Translation.International journal of molecular sciences · 2025Review
- Experimental Animal Models of Phenylketonuria: Pros and Cons.International journal of molecular sciences · 2025Review
- CRISPR Technology Acts as a Dual-Purpose Tool in Pig Breeding: Enhancing Both Agricultural Productivity and Biomedical Applications.Biomolecules · 2024Review
- Low-dose brain radiation: lowering hyperphosphorylated-tau without increasing DNA damage or oncogenic activation.Scientific reports · 2023Article
- Inactivation of growth differentiation factor 9 blocks folliculogenesis in pigs†.Biology of reproduction · 2023Article
- Review
- Production of MSTN knockout porcine cells using adenine base-editing-mediated exon skipping.In vitro cellular & developmental biology. Animal · 2023Article
- Production of Genetically Modified Porcine Embryos via Lipofection of Zona-Pellucida-Intact Oocytes Using the CRISPR/Cas9 System.Animals : an open access journal from MDPI · 2023Article
- The landscape of CRISPR/Cas9 for inborn errors of metabolism.Molecular genetics and metabolism · 2023Review
- Future of biomedical, agricultural, and biological systems research using domesticated animals.Biology of reproduction · 2022Article
- Advances in pig models of human diseases.Animal models and experimental medicine · 2022Review
- CRISPR/Cas9-editing ofFrontiers in genetics · 2022Article
- Review
- Current status of the application of gene editing in pigs.The Journal of reproduction and development · 2021Review
- Phenylketonuria.Nature reviews. Disease primers · 2021Review
- The Potential of CRISPR/Cas9 Gene Editing as a Treatment Strategy for Inherited Diseases.Frontiers in cell and developmental biology · 2021Review
- The effects of early-treated phenylketonuria on volumetric measures of the cerebellum.Molecular genetics and metabolism reports · 2020Article
Corrections and comments
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Authors and funding
26 authors at 5 institutions in 2 countries.
Funding
Abstract
Phenylalanine hydroxylase-deficient (PAH-deficient) phenylketonuria (PKU) results in systemic hyperphenylalaninemia, leading to neurotoxicity with severe developmental disabilities. Dietary phenylalanine (Phe) restriction prevents the most deleterious effects of hyperphenylalaninemia, but adherence to diet is poor in adult and adolescent patients, resulting in characteristic neurobehavioral phenotypes. Thus, an urgent need exists for new treatments. Additionally, rodent models of PKU do not adequately reflect neurocognitive phenotypes, and thus there is a need for improved animal models. To this end, we have developed PAH-null pigs. After selection of optimal CRISPR/Cas9 genome-editing reagents by using an in vitro cell model, zygote injection of 2 sgRNAs and Cas9 mRNA demonstrated deletions in preimplantation embryos, with embryo transfer to a surrogate leading to 2 founder animals. One pig was heterozygous for a PAH exon 6 deletion allele, while the other was compound heterozygous for deletions of exon 6 and of exons 6-7. The affected pig exhibited hyperphenylalaninemia (2000-5000 μM) that was treatable by dietary Phe restriction, consistent with classical PKU, along with juvenile growth retardation, hypopigmentation, ventriculomegaly, and decreased brain gray matter volume. In conclusion, we have established a large-animal preclinical model of PKU to investigate pathophysiology and to assess new therapeutic interventions.
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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.