ArticleScience translational medicine2016
Curative ex vivo liver-directed gene therapy in a pig model of hereditary tyrosinemia type 1.
Article in Science translational medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
43 citing papers in PubMed, 77 citations in OpenAlex.
- Genetically engineered porcine liver: a new era in transplantation.International journal of surgery (London, England) · 2026Article
- Morphological characterization of a novel model of steatohepatitis in theVeterinary pathology · 2026Article
- A pig model of human radiation-induced veno-occlusive liver disease reveals ferroptosis as a therapeutic target.Cell reports. Medicine · 2026Article
- Achieving scalable expansion of therapeutic porcine hepatocytes in vivo through serial transplantation.Animal models and experimental medicine · 2025Article
- Single-cell multi-omics deciphers hepatocyte dedifferentiation and illuminates maintenance strategies.Cell proliferation · 2025Article
- Genetic engineering drives the breakthrough of pig models in liver disease research.Liver research (Beijing, China) · 2024Review
- Ex vivo gene editing and cell therapy for hereditary tyrosinemia type 1.Hepatology communications · 2024Article
- Human Hepatocyte Transplantation: Three Decades of Clinical Experience and Future Perspective.Stem cells translational medicine · 2024Review
- State-of-the-art 2023 on gene therapy for phenylketonuria.Journal of inherited metabolic disease · 2024Review
- Ex vivo factor VIII-modified proliferating human hepatocytes therapy for haemophilia A.Cell proliferation · 2023Article
- Partial Thyroid Hormone-Binding Globulin Deficiency: A Case Report and Literature Review.Diabetes, metabolic syndrome and obesity : targets and therapy · 2023Article
- In vivo lentiviral vector gene therapy to cure hereditary tyrosinemia type 1 and prevent development of precancerous and cancerous lesions.Nature communications · 2022Article
- Generation of immunodeficient pig with hereditary tyrosinemia type 1 and their preliminary application for humanized liver.Cell & bioscience · 2022Article
- Development ofFrontiers in immunology · 2022Article
- Hepatocyte cultures: From collagen gel sandwiches to microfluidic devices with integrated biosensors.APL bioengineering · 2021Review
- Fumarylacetoacetate hydrolase gene as a knockout target for hepatic chimerism and donor liver production.Stem cell reports · 2021Review
- Genetic and Cellular Contributions to Liver Regeneration.Cold Spring Harbor perspectives in biology · 2021Article
- A brief review of reporter gene imaging in oncolytic virotherapy and gene therapy.Molecular therapy oncolytics · 2021Review
- Direct conversion of porcine primary fibroblasts into hepatocyte-like cells.Scientific reports · 2021Article
- CRISPR/Cas9-Mediated Gene Correction in Newborn Rabbits with Hereditary Tyrosinemia Type I.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 5 institutions in 1 country.
Funding
Abstract
We tested the hypothesis that ex vivo hepatocyte gene therapy can correct the metabolic disorder in fumarylacetoacetate hydrolase-deficient (Fah(-/-)) pigs, a large animal model of hereditary tyrosinemia type 1 (HT1). Recipient Fah(-/-) pigs underwent partial liver resection and hepatocyte isolation by collagenase digestion. Hepatocytes were transduced with one or both of the lentiviral vectors expressing the therapeutic Fah and the reporter sodium-iodide symporter (Nis) genes under control of the thyroxine-binding globulin promoter. Pigs received autologous transplants of hepatocytes by portal vein infusion. After transplantation, the protective drug 2-(2-nitro-4-trifluoromethylbenzyol)-1,3 cyclohexanedione (NTBC) was withheld from recipient pigs to provide a selective advantage for expansion of corrected FAH(+) cells. Proliferation of transplanted cells, assessed by both immunohistochemistry and noninvasive positron emission tomography imaging of NIS-labeled cells, demonstrated near-complete liver repopulation by gene-corrected cells. Tyrosine and succinylacetone levels improved to within normal range, demonstrating complete correction of tyrosine metabolism. In addition, repopulation of the Fah(-/-) liver with transplanted cells inhibited the onset of severe fibrosis, a characteristic of nontransplanted Fah(-/-) pigs. This study demonstrates correction of disease in a pig model of metabolic liver disease by ex vivo gene therapy. To date, ex vivo gene therapy has only been successful in small animal models. We conclude that further exploration of ex vivo hepatocyte genetic correction is warranted for clinical use.
Indexed as
Identifiers
What OpenQuestion holds
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.