Overview

• Scientists at University Medical Center Utrecht applied a DdCBE mitochondrial base editor to correct harmful mutations in liver organoids and patient-derived fibroblasts
• The DdCBE system enables single-letter cytosine-to-thymine conversions in mitochondrial DNA without creating double-strand breaks
• Delivering the editor as mRNA within lipid nanoparticles increased editing efficiency and reduced cellular toxicity compared to DNA plasmid methods
• Comprehensive analyses showed negligible off-target changes in nuclear DNA and high precision within mitochondrial genomes
• Researchers note that overcoming challenges in delivering base editors efficiently to affected organs remains a critical step toward clinical application