ArticleScience translational medicine2016
A universal system to select gene-modified hepatocytes in vivo.
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 35 papers.
What it found
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Who cites it
35 citing papers in PubMed, 47 citations in OpenAlex.
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- Repair Drive improves gene editing in the liver.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Targeted Gene Insertion: The Cutting Edge of CRISPR Drug Development with Hemophilia as a Highlight.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Review
- Lethality rescue and long-term amelioration of a citrullinemia type I mouse model by neonatal gene-targeting combined to SaCRISPR-Cas9.Molecular therapy. Methods & clinical development · 2023Article
- Intrabiliary infusion of naked DNA vectors targets periportal hepatocytes in mice.Molecular therapy. Methods & clinical development · 2022Article
- Self-cleaving guide RNAs enable pharmacological selection of precise gene editing events in vivo.Nature communications · 2022Article
- Versatile enzymology and heterogeneous phenotypes in cobalamin complementation type C disease.iScience · 2022Review
- Enhanced genome editing to ameliorate a genetic metabolic liver disease through co-delivery of adeno-associated virus receptor.Science China. Life sciences · 2022Article
- Article
- Cell and Tissue Therapy for the Treatment of Chronic Liver Disease.Annual review of biomedical engineering · 2021Review
- Role of Noncoding RNAs in Acetaminophen-Induced Liver Injury.Gene expression · 2021Review
- Therapeutic liver repopulation by transient acetaminophen selection of gene-modified hepatocytes.Science translational medicine · 2021Article
- Promoterless, Nuclease-Free Genome Editing Confers a Growth Advantage for Corrected Hepatocytes in Mice With Methylmalonic Acidemia.Hepatology (Baltimore, Md.) · 2021Article
- CRISPR/Cas-Dependent and Nuclease-FreeHuman gene therapy · 2021Review
- The Role of Recombinant AAV in Precise Genome Editing.Frontiers in genome editing · 2021Review
- Review
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- Gene Therapy for Methylmalonic Acidemia: Past, Present, and Future.Human gene therapy · 2019Review
- Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Many genetic and acquired liver disorders are amenable to gene and/or cell therapy. However, the efficiencies of cell engraftment and stable genetic modification are low and often subtherapeutic. In particular, targeted gene modifications from homologous recombination are rare events. These obstacles could be overcome if hepatocytes that have undergone genetic modification were to be selectively amplified or expanded. We describe a universally applicable system for in vivo selection and expansion of gene-modified hepatocytes in any genetic background. In this system, the therapeutic transgene is coexpressed with a short hairpin RNA (shRNA) that confers modified hepatocytes with resistance to drug-induced toxicity. An shRNA against the tyrosine catabolic enzyme 4-OH-phenylpyruvate dioxygenase protected hepatocytes from 4-[(2-carboxyethyl)-hydroxyphosphinyl]-3-oxobutyrate, a small-molecule inhibitor of fumarylacetoacetate hydrolase. To select for specific gene targeting events, the protective shRNA was embedded in a microRNA and inserted into a recombinant adeno-associated viral vector designed to integrate site-specifically into the highly active albumin locus. After selection of the gene-targeted cells, transgene expression increased 10- to 1000-fold, reaching supraphysiological levels of human factor 9 protein (50,000 ng/ml) in mice. This drug resistance system can be used to achieve therapeutically relevant transgene levels in hepatocytes in any setting.
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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.