Advances in Mitochondrial Genome Editing for Disease Modeling and Precision Therapeutics
DOI:
https://doi.org/10.64149/J.Carcinog.24.10s.709-723Keywords:
mitochondria, non-infectious diseases, inflammation, precision medicine, mitochondrial diseses, mtDNAAbstract
Mitochondria play a pivotal role in cellular energetics and metabolism, housing their own distinct genome, the mitochondrial DNA (mtDNA). Dysregulation or mutations in mitochondrial genes can lead to a spectrum of diseases, including inherited mitochondrial disorders, neurodegenerative conditions, and age-related disorders. The emerging field of mitochondrial genome editing has garnered attention as a potential avenue for therapeutic interventions and disease modeling.
This review comprehensively explores the diverse approaches and technologies employed in mitochondrial genome editing. It delves into the mechanisms, applications, and challenges associated with using various molecular tools such as mitochondrial gene editing by CRISPR/Cas9 and CRISPR/Cas12a systems, zinc finger nucleases (ZFN), high-fidelity DdCBEs, transcription activator-like effectors nuclease (TALEN), pAgo-based systems, and mitochondrial DNA base editing for therapeutic and disease modeling purposes.
Furthermore, the review sheds light on the potential applications of mitochondrial genome editing in the context of treating mitochondrial diseases, correcting pathogenic variants, and modeling disease pathogenesis for research purposes. Additionally, the discussions encompass the strategies for optimizing specificities, enhancing on-target editing, and addressing potential off-target effects to ensure the clinical translatability of mitochondrial genome editing.
The insights gleaned from this review provide a comprehensive understanding of the current landscape of mitochondrial genome editing, presenting promising avenues for the development of novel therapeutic interventions and disease modeling for various mitochondrial disorders and related conditions.
Overall, this comprehensive review presents a thorough overview of the complexities, opportunities, and future prospects in the field of mitochondrial genome editing, offering a roadmap for advancing the understanding and clinical applications of these innovative technologies.
