ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021
Correction of a urea cycle defect after ex vivo gene editing of human hepatocytes.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
- Targeted gene editing ofMolecular therapy. Nucleic acids · 2026Article
- Spatial profiling of gene editing by in situ sequencing in mice and macaques.Nature biomedical engineering · 2026Article
- Cell therapy for liver disorders: past, present and future.Nature reviews. Gastroenterology & hepatology · 2025Review
- Customizable virus-like particles deliver CRISPR-Cas9 ribonucleoprotein for effective ocular neovascular and Huntington's disease gene therapy.Nature nanotechnology · 2025Article
- Advanced delivery systems for gene editing: A comprehensive review from the GenE-HumDi COST Action Working Group.Molecular therapy. Nucleic acids · 2025Review
- Normothermic Machine Perfusion of Explanted Human Metabolic Livers: A Proof of Concept for Studying Inborn Errors of Metabolism.Journal of inherited metabolic disease · 2025Article
- Characterization and treatment monitoring of ureagenesis disorders using stable isotopes.npj metabolic health and disease · 2025Article
- Research progress of stem cells in the treatment of atherosclerosis.Frontiers in cell and developmental biology · 2025Review
- Mice Engrafted with Human Liver Cells.Seminars in liver disease · 2024Review
- Ammonia-induced stress response in liver disease progression and hepatic encephalopathy.Nature reviews. Gastroenterology & hepatology · 2024Review
- Exploring RNA therapeutics for urea cycle disorders.Journal of inherited metabolic disease · 2024Review
- Ex vivo gene editing and cell therapy for hereditary tyrosinemia type 1.Hepatology communications · 2024Article
- Article
- Diagnostic and Management Issues in Patients with Late-Onset Ornithine Transcarbamylase Deficiency.Children (Basel, Switzerland) · 2023Review
- Genetic Therapy Approaches for Ornithine Transcarbamylase Deficiency.Biomedicines · 2023Review
- Novel Gene-Correction-Based Therapeutic Modalities for Monogenic Liver Disorders.Bioengineering (Basel, Switzerland) · 2022Review
- Electroporation-Mediated Delivery of Cas9 Ribonucleoproteins Results in High Levels of Gene Editing in Primary Hepatocytes.The CRISPR journal · 2022Article
- G Protein-Coupled Receptor GPR35 Suppresses Lipid Accumulation in Hepatocytes.ACS pharmacology & translational science · 2021Article
- Primary human hepatocyte gene editing: Prometheus' chains are loosening.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Synthetic human livers for modeling metabolic diseases.Current opinion in gastroenterology · 2021Review
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Authors and funding
24 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ornithine transcarbamylase deficiency (OTCD) is a monogenic disease of ammonia metabolism in hepatocytes. Severe disease is frequently treated by orthotopic liver transplantation. An attractive approach is the correction of a patient's own cells to regenerate the liver with gene-repaired hepatocytes. This study investigates the efficacy and safety of ex vivo correction of primary human hepatocytes. Hepatocytes isolated from an OTCD patient were genetically corrected ex vivo, through the deletion of a mutant intronic splicing site achieving editing efficiencies >60% and the restoration of the urea cycle in vitro. The corrected hepatocytes were transplanted into the liver of FRGN mice and repopulated to high levels (>80%). Animals transplanted and liver repopulated with genetically edited patient hepatocytes displayed normal ammonia, enhanced clearance of an ammonia challenge and OTC enzyme activity, as well as lower urinary orotic acid when compared to mice repopulated with unedited patient hepatocytes. Gene expression was shown to be similar between mice transplanted with unedited or edited patient hepatocytes. Finally, a genome-wide screening by performing CIRCLE-seq and deep sequencing of >70 potential off-targets revealed no unspecific editing. Overall analysis of disease phenotype, gene expression, and possible off-target editing indicated that the gene editing of a severe genetic liver disease was safe and effective.
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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.