Core Insights - Mitochondrial DNA (mtDNA) plays a crucial role in energy production within cells and is associated with various diseases when mutations occur [6][7] - Recent advancements in gene editing technologies have led to the development of new tools for mtDNA manipulation, emphasizing the importance of effective delivery systems for successful mitochondrial therapies [7][19] Group 1: Mitochondrial Function and Disease - Mitochondria are semi-autonomous organelles that generate ATP and contain circular mtDNA, which encodes essential components for mitochondrial function [1] - Primary mitochondrial diseases (PMD) arise from disruptions in mtDNA or nuclear genes, leading to complex multi-organ dysfunctions that are often difficult to treat [1][6] Group 2: Gene Editing Tools and Delivery Technologies - The review discusses various mitochondrial gene editing tools suitable for different genetic backgrounds and highlights current cytoplasmic targeting delivery technologies [3][7] - Targeting mtDNA for gene editing is challenging due to its double-membrane structure, which limits the efficiency of gene modification [2][3] - Innovative mitochondrial-targeted delivery technologies aim to bypass membrane barriers to enhance the delivery of transgenes/proteins directly to the mitochondrial matrix [3][19] Group 3: Future Directions and Potential - Continuous development of efficient and safe mitochondrial gene editing tools, along with patient-specific delivery carriers, is essential for advancing this field [19] - The potential of innovative mitochondrial-targeted delivery technologies could significantly improve the accessibility of mtDNA, facilitating research and therapeutic applications in mitochondrial genetics [19]