Correction of pathogenic mitochondrial DNA in patient-derived disease models using mitochondrial base editors.

ABSTRACT: Mutations in the mitochondrial genome can cause maternally inherited diseases, cancer, and aging-related conditions. Recent technological progress now enables the creation and correction of mutations in the mitochondrial genome, but it remains relatively unknown how patients with primary mitochondrial disease can benefit from this technology. Here, we demonstrate the potential of the double-stranded DNA deaminase toxin A-derived cytosine base editor (DdCBE) to develop disease models and therapeutic strategies for mitochondrial disease in primary human cells. Introduction of the m.15150G > A mutation in liver organoids resulted in organoid lines with varying degrees of heteroplasmy and correspondingly reduced ATP production, providing a unique model to study functional consequences of diffe

SUBMITTER: Joore IP 

PROVIDER: S-EPMC12186987 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature