Overview

• Researchers in the Netherlands used a DdCBE tool to convert cytosine to thymine in mitochondrial DNA without creating double-stranded breaks.
• The team corrected pathogenic mutations in patient-derived liver organoids and skin cells from a Gitelman-like syndrome patient, restoring key signs of healthy mitochondrial function.
• Encapsulating mRNA encoding the base editor in lipid nanoparticles enhanced delivery efficiency and reduced cellular toxicity compared with DNA-based methods.
• Comprehensive genomic analyses showed negligible off-target edits in the nuclear genome and only minimal unintended changes in mitochondrial DNA.
• Researchers are now tackling in vivo delivery hurdles to target mitochondrial base editors to organs such as muscle and brain ahead of clinical application