ArticleJournal of hepatology2021
Synthetic human ABCB4 mRNA therapy rescues severe liver disease phenotype in a BALB/c.Abcb4
Article in Journal of hepatology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 70 citations in OpenAlex.
- Gene therapy for liver diseases: methods, challenges and opportunities.Journal of nanobiotechnology · 2026Review
- RNA-Based Therapies for Inherited Metabolic Disorders.Journal of inherited metabolic disease · 2026Review
- A Rare Nonsense Mutation in theJournal of clinical medicine · 2026Article
- Targeted metabolomics reveals serum biomarkers and metabolic alterations in cholesterol gallstone patients.Scientific reports · 2026Article
- Functional inactivation of MDR3 caused by a homozygousFrontiers in genetics · 2026Article
- Bile Acid Detergency as Determinant of Liver Pathology in a Humanized Mouse Model of Progressive Familial Intrahepatic Cholestasis Type 3.Cellular and molecular gastroenterology and hepatology · 2026Article
- Cholestasis in Alcohol-Associated Liver Disease.The American journal of pathology · 2026Review
- Delivering the Message: Translating mRNA Therapy for Liver Inherited Metabolic Diseases.Journal of inherited metabolic disease · 2025Review
- Review
- Gasdermin D aggravates a mouse model of radiation-induced liver disease by promoting chemokine secretion and neutrophil recruitment.Nature communications · 2025Article
- Clinical, genetic and functional perspectives on ATP-binding cassette subfamily B member 4 variants in five cholestasis adults.World journal of gastroenterology · 2025Article
- One Family with Cholestasis: The Twisted Road to the Diagnosis of Pfic 3-Three Case Reports.Reports (MDPI) · 2025Article
- Impact of liver fibrosis on AAV-mediated gene transfer to mouse hepatocytes.Nature communications · 2025Article
- LncRNAs, RNA Therapeutics, and Emerging Technologies in Liver Pathobiology.Seminars in liver disease · 2025Review
- Identification of novel ABCB4 variants and genotype-phenotype correlation in progressive familial intrahepatic cholestasis type 3.Scientific reports · 2024Article
- mRNA-delivery of IDO1 suppresses T cell-mediated autoimmunity.Cell reports. Medicine · 2024Article
- Lipid-nanoparticle-enabled nucleic acid therapeutics for liver disorders.Acta pharmaceutica Sinica. B · 2024Review
- Frameworks for transformational breakthroughs in RNA-based medicines.Nature reviews. Drug discovery · 2024Review
- Molecular Insights of Cholestasis in MDR2 Knockout Murine Liver Organoids.Journal of proteome research · 2024Article
- Genetics of Gallstone Disease and Their Clinical Significance: A Narrative Review.Journal of clinical and translational hepatology · 2024Review
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Authors and funding
20 authors at 4 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsProgressive familial intrahepatic cholestasis type 3 (PFIC3) is a rare lethal autosomal recessive liver disorder caused by loss-of-function variations of the ABCB4 gene, encoding a phosphatidylcholine transporter (ABCB4/MDR3). Currently, no effective treatment exists for PFIC3 outside of liver transplantation.
methodsWe have produced and screened chemically and genetically modified mRNA variants encoding human ABCB4 (hABCB4 mRNA) encapsulated in lipid nanoparticles (LNPs). We examined their pharmacological effects in a cell-based model and in a new in vivo mouse model resembling human PFIC3 as a result of homozygous disruption of the Abcb4 gene in fibrosis-susceptible BALB/c.Abcb4
resultsWe show that treatment with liver-targeted hABCB4 mRNA resulted in de novo expression of functional hABCB4 protein and restored phospholipid transport in cultured cells and in PFIC3 mouse livers. Importantly, repeated injections of the hABCB4 mRNA effectively rescued the severe disease phenotype in young Abcb4
conclusionsOur data provide strong preclinical proof-of-concept for hABCB4 mRNA therapy as a potential treatment option for patients with PFIC3. LAY SUMMARY: This report describes the development of an innovative mRNA therapy as a potential treatment for PFIC3, a devastating rare paediatric liver disease with no treatment options except liver transplantation. We show that administration of our mRNA construct completely rescues severe liver disease in a genetic model of PFIC3 in mice.
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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.