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

doi:10.1016/j.ymthe.2026.06.044

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Article

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

Molecular therapy : the journal of the American Society of Gene Therapy - 2 Sept 2026

Ginn Samantha L, Doroudian Fatemeh, Christina Sharntie, Chan Otilia P Y, Lucas Caitlin W, Zhu Erhua, Yang Sile F, Devanapalli Beena, Klein Anne H, Scott Suzanne, Vitale Joseph, Cunningham Sharon C, Liao Sophia H Y, Cabanes-Creus Marti, Lisowski Leszek, Alexander Ian E

Abstract excerpt

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...

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Topics

Animals
Humans
Mice
Hepatocytes
Ornithine Carbamoyltransferase

Methodology Data sources Editorial policy Privacy Delete account & data About Contact Helena Bioinformatics

Dependovirus

Gene Editing

Phenotype

CRISPR-Cas Systems

Ornithine Carbamoyltransferase Deficiency Disease

Genetic Vectors

Mutation

Disease Models, Animal

Genetic Loci

Liver

Gene Expression Regulation

Source

Open in PubMed Open full text

Identifiers

PMID: 42427028
DOI: 10.1016/j.ymthe.2026.06.044
PMCID: PMC13555538

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Functional editing of the OTC locus by targeted integration with phenotype correction and restoration of endogenous expression patterns.PMID 42427028Read ↗

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