Evidence map›Paper›PMID 31303505›Full record

ArticleEBioMedicine2019

Long-term efficacy and safety of mRNA therapy in two murine models of methylmalonic acidemia.

Ding An, Andrea Frassetto, Eric Jacquinet, Marianne Eybye, Joseph Milano, Christine DeAntonis, Vi Nguyen, Rodrigo Laureano, Jaclyn Milton, Staci Sabnis and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 1 pooled it
4.5field-weighted citation impact, top 5% 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

55 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.

  1. Pooled it
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  4. RNA-Based Therapies for Inherited Metabolic Disorders.Journal of inherited metabolic disease · 2026
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  16. The advent of clinical self-amplifying RNA vaccines.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 1 institution in 1 country.

Ding AnModerna, Inc., 200 Technology Square, Cambridge, MA 02139, USA.
Andrea FrassettoModerna, Inc., 200 Technology Square, Cambridge, MA 02139, USA.
Eric JacquinetModerna, Inc., 200 Technology Square, Cambridge, MA 02139, USA.
Marianne EybyeModerna, Inc., 200 Technology Square, Cambridge, MA 02139, USA.
Joseph MilanoModerna, Inc., 200 Technology Square, Cambridge, MA 02139, USA.
Christine DeAntonisModerna, Inc., 200 Technology Square, Cambridge, MA 02139, USA.
Vi NguyenModerna, Inc., 200 Technology Square, Cambridge, MA 02139, USA.
Rodrigo LaureanoModerna, Inc., 200 Technology Square, Cambridge, MA 02139, USA.
Jaclyn MiltonModerna, Inc., 200 Technology Square, Cambridge, MA 02139, USA.
Staci SabnisModerna, Inc., 200 Technology Square, Cambridge, MA 02139, USA.
Christine M LukacsModerna, Inc., 200 Technology Square, Cambridge, MA 02139, USA.
Lin T GueyModerna, Inc., 200 Technology Square, Cambridge, MA 02139, USA. Electronic address: Lin.Guey@Modernatx.com.
Moderna Therapeutics (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIsolated methylmalonic acidemia/aciduria (MMA) is an ultra-rare, serious, inherited metabolic disorder with significant morbidity and mortality. Exogenously delivered mRNA encoding human methylmalonyl-CoA mutase (hMUT), the enzyme most frequently mutated in MMA, is a potential therapy to produce functional MUT enzyme in liver.

methodsTwo 12-week repeat-dose studies were conducted to evaluate the efficacy and safety of intravenously-administered hMUT mRNA encapsulated in lipid nanoparticles in two murine models of MMA.

findingsIn MMA hypomorphic mice, hMUT mRNA treatment resulted in dose-dependent and reproducible biomarker responses after each dose. Enzymatically-active MUT protein was produced in liver in a dose-dependent manner. hMUT mRNA was well-tolerated with no adverse effects, as indicated by the lack of clinical observations, minimal changes in clinical chemistry parameters, and histopathology examination across all tissues. In severe MMA mice, hMUT mRNA led to substantially improved survival and growth and ameliorated biochemical abnormalities, all of which are cardinal clinical manifestations in severely affected patients.

interpretationThese data demonstrate durable functional benefit of hMUT mRNA and support development of this new class of therapy for a devastating, pediatric disorder. FUND: This work was funded by Moderna, Inc.

Indexed as

Amino Acid Metabolism, Inborn ErrorsAnimalsChildDisease Models, AnimalHumansLipidsLiverMethylmalonyl-CoA MutaseMiceRNA, MessengerLipidsMethylmalonyl-CoA MutaseRNA, MessengerEnzyme replacementLiver targeted therapyMethylmalonyl-CoA mutaseOrganic acidemiaSystemic mRNA therapy

Identifiers

PMID31303505
PMCPMC6642332
OpenAlexW2960789951

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.