Trends and prospects in mitochondrial genome editing

초록

Mitochondria are of fundamental importance in programmed cell death, cellular metabolism, and intracellular calcium concentration modulation, and inheritable mitochondrial disorders via mitochondrial DNA (mtDNA) mutation cause several diseases in various organs and systems. Nevertheless, mtDNA editing, which plays an essential role in the treatment of mitochondrial disorders, still faces several challenges. Recently, programmable editing tools for mtDNA base editing, such as cytosine base editors derived from DddA (DdCBEs), transcription activator-like effector (TALE)-linked deaminase (TALED), and zinc finger deaminase (ZFD), have emerged with considerable potential for correcting pathogenic mtDNA variants. In this review, we depict recent advances in the field, including structural biology and repair mechanisms, and discuss the prospects of using base editing tools on mtDNA to broaden insight into their medical applicability for treating mitochondrial diseases. Gene editing: moving into mitochondriaApplying gene editing techniques to the DNA found within mitochondria, the intracellular energy-producing organelles, is being explored as an approach to treating various diseases. Most of the cell's genetic information is found in the nucleus, but mitochondria carry their own set of genes. Hong Thi Lam Phan Korea University, Seoul, South Korea, and coworkers review current trends and prospects in mitochondrial gene editing. Genetic defects in mitochondria have been implicated in many diseases, mainly affecting muscle and nervous tissues. A variety of methods for editing mitochondrial DNA are being explored, both as possible treatments and as methods to create animal models of human mitochondrial diseases. Challenges yet to be overcome, initially in animal studies, including finding effective means to deliver the molecular editing tools into mitochondria and achieving therapeutic results without harmful side effects.

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