Wang Yi, Yang Jing-Song, Zhao Min, Chen Jia-Qi, Xie Hai-Xin, Yu Hao-Yuan, Liu Na-Hui, Yi Zi-Juan, Liang Hui-Lin, Xing Lei, Jiang Hu-Lin
State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China.
State Key Laboratory of Natural Medicines, Department of Pharmaceutics, China Pharmaceutical University, Nanjing 210009, China; College of Pharmacy, Yanbian University, Yanji 133002, China.
Adv Drug Deliv Rev. 2024 Aug;211:115355. doi: 10.1016/j.addr.2024.115355. Epub 2024 Jun 5.
Mitochondrial genome (mtDNA) independent of nuclear gene is a set of double-stranded circular DNA that encodes 13 proteins, 2 ribosomal RNAs and 22 mitochondrial transfer RNAs, all of which play vital roles in functions as well as behaviors of mitochondria. Mutations in mtDNA result in various mitochondrial disorders without available cures. However, the manipulation of mtDNA via the mitochondria-targeted gene delivery faces formidable barriers, particularly owing to the mitochondrial double membrane. Given the fact that there are various transport channels on the mitochondrial membrane used to transfer a variety of endogenous substances to maintain the normal functions of mitochondria, mitochondrial endogenous substance transport-inspired nanomaterials have been proposed for mitochondria-targeted gene delivery. In this review, we summarize mitochondria-targeted gene delivery systems based on different mitochondrial endogenous substance transport pathways. These are categorized into mitochondrial steroid hormones import pathways-inspired nanomaterials, protein import pathways-inspired nanomaterials and other mitochondria-targeted gene delivery nanomaterials. We also review the applications and challenges involved in current mitochondrial gene editing systems. This review delves into the approaches of mitochondria-targeted gene delivery, providing details on the design of mitochondria-targeted delivery systems and the limitations regarding the various technologies. Despite the progress in this field is currently slow, the ongoing exploration of mitochondrial endogenous substance transport and mitochondrial biological phenomena may act as a crucial breakthrough in the targeted delivery of gene into mitochondria and even the manipulation of mtDNA.
线粒体基因组（mtDNA）独立于核基因，是一组双链环状DNA，编码13种蛋白质、2种核糖体RNA和22种线粒体转运RNA，所有这些在维持线粒体功能和行为方面都起着至关重要的作用。mtDNA突变会导致各种线粒体疾病，目前尚无有效治疗方法。然而，通过线粒体靶向基因递送对mtDNA进行操作面临巨大障碍，尤其是由于线粒体的双层膜结构。鉴于线粒体膜上存在各种转运通道，用于转运多种内源性物质以维持线粒体的正常功能，受线粒体内源性物质转运启发的纳米材料已被提出用于线粒体靶向基因递送。在这篇综述中，我们总结了基于不同线粒体内源性物质转运途径的线粒体靶向基因递送系统。这些系统可分为受线粒体甾体激素导入途径启发的纳米材料、受蛋白质导入途径启发的纳米材料以及其他线粒体靶向基因递送纳米材料。我们还综述了当前线粒体基因编辑系统所涉及的应用和挑战。这篇综述深入探讨了线粒体靶向基因递送的方法，详细介绍了线粒体靶向递送系统的设计以及各种技术的局限性。尽管该领域目前进展缓慢，但对线粒体内源性物质转运和线粒体生物学现象的持续探索可能成为将基因靶向递送至线粒体乃至操纵mtDNA的关键突破。
