ArticleMolecular therapy : the journal of the American Society of Gene Therapy2019
mRNA Therapy Improves Metabolic and Behavioral Abnormalities in a Murine Model of Citrin Deficiency.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 72 citations in OpenAlex.
- Peptide additives reprogram the lipid nanoparticle corona and enhance gene delivery in a serum-free environment for lung epithelium.bioRxiv : the preprint server for biology · 2026Article
- 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
- Review
- Delivering the Message: Translating mRNA Therapy for Liver Inherited Metabolic Diseases.Journal of inherited metabolic disease · 2025Review
- Review
- Current Understanding of Pathogenic Mechanisms and Disease Models of Citrin Deficiency.Journal of inherited metabolic disease · 2025Review
- Beginning of a new era of synthetic messenger RNA therapeutics: Comprehensive insights on mRNA drug design, development and applications.Experimental biology and medicine (Maywood, N.J.) · 2025Review
- The therapeutic landscape of citrin deficiency.Journal of inherited metabolic disease · 2024Review
- Exploring RNA therapeutics for urea cycle disorders.Journal of inherited metabolic disease · 2024Review
- 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
- Non-viral and viral delivery systems for hemophilia A therapy: recent development and prospects.Annals of hematology · 2024Review
- Ultrasound-mediated gene delivery specifically targets liver sinusoidal endothelial cells for sustained FVIII expression in hemophilia A mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Adult-onset Type II Citrullinemia Developed under Dietary Restrictions during Imprisonment.Internal medicine (Tokyo, Japan) · 2024Article
- Hyperammonemia and inborn errors of metabolism.Translational pediatrics · 2024Article
- Host sex disparity and viral genotype dependence of the glycosylation level of small Hepatitis B surface protein in patients with HBeAg-positive chronic Hepatitis B.Virology journal · 2023Article
- Exogenous aralar/slc25a12 can replace citrin/slc25a13 as malate aspartate shuttle component in liver.Molecular genetics and metabolism reports · 2023Article
- Amnio acid substitution at position 298 of human glucose-6 phosphatase-α significantly impacts its stability in mammalian cells.Amino acids · 2023Article
- Development of a Library of Disulfide Bond-Containing Cationic Lipids for mRNA Delivery.Pharmaceutics · 2023Article
Corrections and comments
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Authors and funding
27 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Citrin deficiency is an autosomal recessive disorder caused by loss-of-function mutations in SLC25A13, encoding the liver-specific mitochondrial aspartate/glutamate transporter. It has a broad spectrum of clinical phenotypes, including life-threatening neurological complications. Conventional protein replacement therapy is not an option for these patients because of drug delivery hurdles, and current gene therapy approaches (e.g., AAV) have been hampered by immunogenicity and genotoxicity. Although dietary approaches have shown some benefits in managing citrin deficiency, the only curative treatment option for these patients is liver transplantation, which is high-risk and associated with long-term complications because of chronic immunosuppression. To develop a new class of therapy for citrin deficiency, codon-optimized mRNA encoding human citrin (hCitrin) was encapsulated in lipid nanoparticles (LNPs). We demonstrate the efficacy of hCitrin-mRNA-LNP therapy in cultured human cells and in a murine model of citrin deficiency that resembles the human condition. Of note, intravenous (i.v.) administration of the hCitrin-mRNA resulted in a significant reduction in (1) hepatic citrulline and blood ammonia levels following oral sucrose challenge and (2) sucrose aversion, hallmarks of hCitrin deficiency. In conclusion, mRNA-LNP therapy could have a significant therapeutic effect on the treatment of citrin deficiency and other mitochondrial enzymopathies with limited treatment options.
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