Evidence map›Paper›PMID 42427028›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2026

Functional editing of the OTC locus by targeted integration with phenotype correction and restoration of endogenous expression patterns.

Samantha L Ginn, Fatemeh Doroudian, Sharntie Christina, Otilia P Y Chan, Caitlin W Lucas, Erhua Zhu, Sile F Yang, Beena Devanapalli, Anne H Klein, Suzanne Scott and 6 more

Abstract read
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Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

16 authors.

Samantha L GinnGene Therapy Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney and Sydney Children's Hospitals Network, Westmead, NSW 2145, Australia. Electronic address: sginn@cmri.org.au.
Fatemeh DoroudianGene Therapy Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney and Sydney Children's Hospitals Network, Westmead, NSW 2145, Australia.
Sharntie ChristinaGene Therapy Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney and Sydney Children's Hospitals Network, Westmead, NSW 2145, Australia.
Otilia P Y ChanGene Therapy Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney and Sydney Children's Hospitals Network, Westmead, NSW 2145, Australia.
Caitlin W LucasGene Therapy Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney and Sydney Children's Hospitals Network, Westmead, NSW 2145, Australia.
Erhua ZhuGene Therapy Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney and Sydney Children's Hospitals Network, Westmead, NSW 2145, Australia.
Sile F YangGene Therapy Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney and Sydney Children's Hospitals Network, Westmead, NSW 2145, Australia.
Beena DevanapalliNSW Biochemical Genetics Service, The Children's Hospital at Westmead, Westmead, NSW 2145, Australia.
Anne H KleinAustralian e-Health Research Centre, Commonwealth Scientific and Industrial Research Organisation (CSIRO), Herston, QLD 4006, Australia.
Suzanne ScottTranslational Vectorology Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney and Sydney Children's Hospitals Network, Westmead, NSW 2145, Australia.
Joseph VitaleGene Therapy Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney and Sydney Children's Hospitals Network, Westmead, NSW 2145, Australia.
Sharon C CunninghamGene Therapy Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney and Sydney Children's Hospitals Network, Westmead, NSW 2145, Australia.
Sophia H Y LiaoGene Therapy Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney and Sydney Children's Hospitals Network, Westmead, NSW 2145, Australia.
Marti Cabanes-CreusTranslational Vectorology Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney and Sydney Children's Hospitals Network, Westmead, NSW 2145, Australia.
Leszek LisowskiTranslational Vectorology Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney and Sydney Children's Hospitals Network, Westmead, NSW 2145, Australia; Laboratory of Molecular Oncology and Innovative Therapies, Military Institute of Medicine, National Research Institute, 04-141 Warszawa, Poland.
Ian E AlexanderGene Therapy Research Unit, Children's Medical Research Institute, Faculty of Medicine and Health, The University of Sydney and Sydney Children's Hospitals Network, Westmead, NSW 2145, Australia; Discipline of Child and Adolescent Health, Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW 2145, Australia.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Here, we report highly efficient functional repair of the ornithine transcarbamylase (OTC) locus in mutant mouse and human hepatocytes in vivo using a dual adeno-associated virus system delivering CRISPR-Cas9 editing reagents and a promoterless donor for targeted integration. The approach was mutation agnostic and targeted intronic sequences to prevent inadvertent inactivation of hypomorphic alleles. Notably, in a murine model, we corrected the metabolic defect and simultaneously achieved liver-wide restoration of physiological metabolic zonation of Otc expression by capturing native cis-acting regulatory elements. The effectiveness of this approach was confirmed using a universally configured therapeutic cassette in patient-derived primary human hepatocytes in vivo. These data provide a powerful template to guide further optimization of this approach and, given the high editing efficacy required for phenotypic effect in OTC deficiency, have broader relevance to other liver disease phenotypes.

Indexed as

Gene EditingGenetic LociOrnithine CarbamoyltransferaseOrnithine Carbamoyltransferase Deficiency DiseaseAnimalsCRISPR-Cas SystemsDependovirusDisease Models, AnimalGene Expression RegulationGenetic VectorsHepatocytesHumansLiverMiceMutationPhenotypeOrnithine CarbamoyltransferaseAAVCRISPR-Cas9HITIlivermetabolic zonationOTC deficiencyprimary human hepatocytestargeted integration

Identifiers

PMID42427028
PMCPMC13555538

What OpenQuestion holds

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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.