ArticleNature communications2020
Dual mRNA therapy restores metabolic function in long-term studies in mice with propionic acidemia.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
What it found
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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.
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Who cites it
78 citing papers in PubMed, 121 citations in OpenAlex.
- Trial
- Inhaled mRNA therapy for treatment of cystic fibrosis: Interim results of a randomized, double-blind, placebo-controlled phase 1/2 clinical study.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2023Trial
- RNA therapeutics: current status and future directions.Signal transduction and targeted therapy · 2026Review
- Precision metabolic therapy for propionic acidemia.Biochemical pharmacology · 2026Review
- Article
- Long Term Follow-Up After Transplantation in Propionic Acidemia: A Retrospective French Pediatric and Adult Cohort Study.Journal of inherited metabolic disease · 2026Article
- Beyond the Sequence: Chemical and Topological Design and Innovations in mRNA Therapeutics.Chemical reviews · 2026Review
- RNA-Based Therapies for Inherited Metabolic Disorders.Journal of inherited metabolic disease · 2026Review
- Tissue-engineered cardiac patches enriched with IGF1 modified mRNA alleviate myocardial infarction by enhancing cell survival and angiogenesis.Materials today. Bio · 2026Article
- The mRNA-Based Innovative Strategy: Progress and Challenges.Nano-micro letters · 2026Review
- Insights into Neutrophil Dysfunction in Inherited Metabolic Disorders.Journal of innate immunity · 2026Review
- mRNA-based therapies: From molecular discovery to clinical revolution.Genetics and molecular biology · 2026Article
- mRNA delivery systems 2.0: Engineering extrahepatic delivery for non-vaccine therapeutics.Materials today. Bio · 2025Review
- Importance and Potential of Rare Disease Research in Pediatric Rheumatology and Beyond: Pushing Frontiers.ACR open rheumatology · 2025Review
- Rational design of lipid nanoparticles for enabling gene therapies.Molecular therapy. Methods & clinical development · 2025Review
- mRNA-based enzyme replacement for propionic acidaemia.Nature reviews. Endocrinology · 2025Article
- Delivering the Message: Translating mRNA Therapy for Liver Inherited Metabolic Diseases.Journal of inherited metabolic disease · 2025Review
- Review
- Clinical burden of propionic acidemia in the United States: a claims-based study by age stratum.Orphanet journal of rare diseases · 2025Article
- Considerations for mRNA Product Development, Regulation and Deployment Across the Lifecycle.Vaccines · 2025Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Propionic acidemia/aciduria (PA) is an ultra-rare, life-threatening, inherited metabolic disorder caused by deficiency of the mitochondrial enzyme, propionyl-CoA carboxylase (PCC) composed of six alpha (PCCA) and six beta (PCCB) subunits. We herein report an enzyme replacement approach to treat PA using a combination of two messenger RNAs (mRNAs) (dual mRNAs) encoding both human PCCA (hPCCA) and PCCB (hPCCB) encapsulated in biodegradable lipid nanoparticles (LNPs) to produce functional PCC enzyme in liver. In patient fibroblasts, dual mRNAs encoded proteins localize in mitochondria and produce higher PCC enzyme activity vs. single (PCCA or PCCB) mRNA alone. In a hypomorphic murine model of PA, dual mRNAs normalize ammonia similarly to carglumic acid, a drug approved in Europe for the treatment of hyperammonemia due to PA. Dual mRNAs additionally restore functional PCC enzyme in liver and thus reduce primary disease-associated toxins in a dose-dependent manner in long-term 3- and 6-month repeat-dose studies in PA mice. Dual mRNAs are well-tolerated in these studies with no adverse findings. These studies demonstrate the potential of mRNA technology to chronically administer multiple mRNAs to produce large complex enzymes, with applicability to other genetic disorders.
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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.