GENOME-BASED THERAPEUTIC STRATEGIES FOR REVERSING MITOCHONDRIAL DNA-ASSOCIATED DISORDERS

Abstract

Background: Mitochondrial DNA (mtDNA)-associated diseases are inherited metabolic disorders caused by pathogenic mutations that disrupt oxidative phosphorylation and cellular energy production. Therapeutic options are limited to symptomatic relief and do not effectively reverse the underlying genetic abnormality.

Objective: To evaluate genome-based therapeutic approaches to correct pathogenic mtDNA mutations and restore mitochondrial function by using advanced genome-editing technologies.

Methodology: A comprehensive genomic and bioinformatics-based analysis was performed on mtDNA data from patient-derived sequences and public genomic repositories. We comparatively analyzed CRISPR-Cas systems, mitochondrial-targeted transcription activator-like effector nucleases (TALENs), zinc-finger nucleases (ZFNs) and mitochondrial replacement therapy (MRT) for their efficiency in reducing mutations, restoring ATP levels and reducing reactive oxygen species (ROS).

Findings: TALEN-mediated editing had the highest mutation reduction efficiency (82%) and significantly improved ATP synthesis (48%), while MRT reduced ROS levels (55%). CRISPR-based approaches showed 74% editing efficiency with enhanced mitochondrial recovery.

Conclusion: The genome-based therapeutic technologies hold great promise in the reversal of mtDNA-associated disorders and the development of precision mitochondrial medicine.