Evidence map›Paper›PMID 37162351›Full record

ArticleHuman molecular genetics2023

Messenger RNA rescues medium-chain acyl-CoA dehydrogenase deficiency in fibroblasts from patients and a murine model.

Xue-Jun Zhao, Ai-Walid Mohsen, Stephanie Mihalik, Keaton Solo, Shakuntala Basu, Ermal Aliu, Huifang Shi, Catherine Kochersberger, Anuradha Karunanidhi, Clinton Van't Land and 9 more

Erratum issuedOpen access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Human molecular genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
2.5field-weighted citation impact, top 11% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 13 citations in OpenAlex.

  1. RNA-Based Therapies for Inherited Metabolic Disorders.Journal of inherited metabolic disease · 2026
    Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. mRNA therapy as primary and bridge therapy for inborn errors of metabolism.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Article
  7. Article
  8. A review of fatty acid oxidation disorder mouse models.Molecular genetics and metabolism · 2024
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 2 institutions in 2 countries.

Xue-Jun ZhaoDivision of Genetic and Genomic Medicine, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, 15224, USA.
Ai-Walid MohsenDivision of Genetic and Genomic Medicine, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, 15224, USA.ORCID 0000-0002-0096-5959
Stephanie MihalikDivision of Genetic and Genomic Medicine, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, 15224, USA.
Keaton SoloDivision of Genetic and Genomic Medicine, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, 15224, USA.
Shakuntala BasuDivision of Genetic and Genomic Medicine, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, 15224, USA.
Ermal AliuDivision of Genetic and Genomic Medicine, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, 15224, USA.
Huifang ShiDivision of Genetic and Genomic Medicine, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, 15224, USA.
Catherine KochersbergerDivision of Genetic and Genomic Medicine, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, 15224, USA.
Anuradha KarunanidhiDivision of Genetic and Genomic Medicine, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, 15224, USA.
Clinton Van't LandDivision of Genetic and Genomic Medicine, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, 15224, USA.
Kimberly A CoughlanModerna Therapeutics, Rare Diseases, Cambridge, MA, 02139, USA.
Summar SiddiquiModerna Therapeutics, Rare Diseases, Cambridge, MA, 02139, USA.
Lisa M RiceModerna Therapeutics, Rare Diseases, Cambridge, MA, 02139, USA.
Shawn HillierModerna Therapeutics, Rare Diseases, Cambridge, MA, 02139, USA.
Eleonora GuadagninModerna Therapeutics, Rare Diseases, Cambridge, MA, 02139, USA.
Christine DeAntonisModerna Therapeutics, Rare Diseases, Cambridge, MA, 02139, USA.
Paloma H GiangrandeModerna Therapeutics, Rare Diseases, Cambridge, MA, 02139, USA.
Paolo G V MartiniModerna Therapeutics, Rare Diseases, Cambridge, MA, 02139, USA.
Jerry VockleyDivision of Genetic and Genomic Medicine, Department of Pediatrics, University of Pittsburgh, Pittsburgh, PA, 15224, USA.
University of Pittsburgh · USModerna Therapeutics (United States) · US

Funding

NIH HHS R01 DK78755
6 · The paper itself

Abstract

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is the most common inherited disorder of mitochondrial fatty acid β-oxidation (FAO) in humans. Patients exhibit clinical episodes often associated with fasting. Symptoms include hypoketotic hypoglycemia and Reye-like episodes. With limited treatment options, we explored the use of human MCAD (hMCAD) mRNA in fibroblasts from patients with MCAD deficiency to provide functional MCAD protein and reverse the metabolic block. Transfection of hMCAD mRNA into MCAD- deficient patient cells resulted in an increased MCAD protein that localized to mitochondria, concomitant with increased enzyme activity in cell extracts. The therapeutic hMCAD mRNA-lipid nanoparticle (LNP) formulation was also tested in vivo in Acadm-/- mice. Administration of multiple intravenous doses of the hMCAD mRNA-LNP complex (LNP-MCAD) into Acadm-/- mice produced a significant level of MCAD protein with increased enzyme activity in liver, heart and skeletal muscle homogenates. Treated Acadm-/- mice were more resistant to cold stress and had decreased plasma levels of medium-chain acylcarnitines compared to untreated animals. Furthermore, hepatic steatosis in the liver from treated Acadm-/- mice was reduced compared to untreated ones. Results from this study support the potential therapeutic value of hMCAD mRNA-LNP complex treatment for MCAD deficiency.

Indexed as

Acyl-CoA DehydrogenasesFibroblastsAcyl-CoA DehydrogenaseAnimalsDisease Models, AnimalHumansLipid Metabolism, Inborn ErrorsMiceRNA, MessengerAcyl-CoA DehydrogenaseAcyl-CoA DehydrogenasesRNA, Messenger

Identifiers

PMID37162351
PMCPMC10321387
OpenAlexW4376121631

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.