Evidence map›Paper›PMID 39799396›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2025

Characterization of a novel conditional knockout mouse model to assess efficacy of mRNA therapy in the context of severe OTC deficiency.

Jenny Zhou, Shi Liang, Ling Yin, Andrea Frassetto, Anne-Renee Graham, Rebecca White, Maria Principe, Madelyn Severson, Tiffany Palmer, Shan Naidu and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. New approach methodologies (NAMs) for preclinical and translational evaluation of mRNA-lipid nanoparticle (LNP) therapeutics.Journal of controlled release : official journal of the Controlled Release Society · 2026
    Review
  2. Review
  3. 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
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

14 authors.

Jenny ZhouModerna, Inc., Cambridge, MA 02142, USA.
Shi LiangModerna, Inc., Cambridge, MA 02142, USA.
Ling YinModerna, Inc., Cambridge, MA 02142, USA.
Andrea FrassettoModerna, Inc., Cambridge, MA 02142, USA.
Anne-Renee GrahamModerna, Inc., Cambridge, MA 02142, USA.
Rebecca WhiteModerna, Inc., Cambridge, MA 02142, USA.
Maria PrincipeModerna, Inc., Cambridge, MA 02142, USA.
Madelyn SeversonModerna, Inc., Cambridge, MA 02142, USA.
Tiffany PalmerModerna, Inc., Cambridge, MA 02142, USA.
Shan NaiduModerna, Inc., Cambridge, MA 02142, USA.
Eric JacquinetModerna, Inc., Cambridge, MA 02142, USA.
Mike ZimmerModerna, Inc., Cambridge, MA 02142, USA.
Patrick F FinnModerna, Inc., Cambridge, MA 02142, USA. Electronic address: patrick.finn@modernatx.com.
Paolo G V MartiniModerna, Inc., Cambridge, MA 02142, USA. Electronic address: paolom67@gmail.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Ornithine transcarbamylase deficiency (OTCD) is the most common urea-cycle disorder, characterized by hyperammonemia and accompanied by a high unmet patient need. mRNA therapies have been shown to be efficacious in hypomorphic Sparse-fur abnormal skin and hair (Spf-ash) mice, a model of late-onset disease. However, studying the efficacy of ornithine transcarbamylase (OTC) mRNA therapy in traditional knockout mice, a model for severe early-onset OTCD, is hampered by the rapid lethality of the model and poor lipid nanoparticle (LNP) uptake into neonatal mouse liver. We developed a novel tamoxifen-inducible mouse to study the effect of mRNA therapy in the context of complete or near-complete OTC loss in adult animals. Characterization of the model showed that it is highly reproducible, 100% penetrant, and phenocopies hallmarks of human disease, with animals exhibiting decreased body weight, hyperammonemia, and brain edema. Delivery of OTC mRNA increased survival, maintained body weight, delayed the onset of hyperammonemia, and reduced brain edema. Therefore, this model provides a platform to study LNP-mediated mRNA therapies for the treatment of late-onset OTCD.

Indexed as

Genetic TherapyOrnithine CarbamoyltransferaseOrnithine Carbamoyltransferase Deficiency DiseaseRNA, MessengerAnimalsDisease Models, AnimalHumansMiceMice, KnockoutNanoparticlesTamoxifenOrnithine CarbamoyltransferaseRNA, MessengerTamoxifenconditional knockoutLNP-mediated deliverymouse modelmRNA therapyornithine transcarbamylase deficiencyOTCOTCD

Identifiers

PMID39799396
PMCPMC11897776

What OpenQuestion holds

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Registered trials

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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.