Correcting OTC Gene Function by Targeted DNA Integration to Restore Normal Activity and Traits

Highly efficient functional repair of the ornithine transcarbamylase (OTC) locus was achieved in mutant mouse and human liver cells in vivo.

• A dual AAV system was used to deliver CRISPR-Cas9 editing tools and a donor for targeted integration.
• The method was mutation agnostic, targeting intronic sequences to avoid inactivation of certain alleles.
• In a mouse model, the metabolic defect was corrected while restoring normal liver function and gene expression.
• The approach was confirmed in human liver cells derived from patients, demonstrating its effectiveness.
• This technique may serve as a basis for optimizing treatments for other liver diseases due to its high editing efficiency.

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