Faria Rúben, Boisguérin Prisca, Sousa Ângela, Costa Diana
CICS-UBI-Health Sciences Research Centre, University of Beira Interior, 6201-506 Covilhã, Portugal.
PhyMedExp, Université de Montpellier, INSERM, CNRS, 34295 Montpellier, France.
Pharmaceutics. 2023 Feb 8;15(2):572. doi: 10.3390/pharmaceutics15020572.
Mitochondria are membrane-bound cellular organelles of high relevance responsible for the chemical energy production used in most of the biochemical reactions of cells. Mitochondria have their own genome, the mitochondrial DNA (mtDNA). Inherited solely from the mother, this genome is quite susceptible to mutations, mainly due to the absence of an effective repair system. Mutations in mtDNA are associated with endocrine, metabolic, neurodegenerative diseases, and even cancer. Currently, therapeutic approaches are based on the administration of a set of drugs to alleviate the symptoms of patients suffering from mitochondrial pathologies. Mitochondrial gene therapy emerges as a promising strategy as it deeply focuses on the cause of mitochondrial disorder. The development of suitable mtDNA-based delivery systems to target and transfect mammalian mitochondria represents an exciting field of research, leading to progress in the challenging task of restoring mitochondria's normal function. This review gathers relevant knowledge on the composition, targeting performance, or release profile of such nanosystems, offering researchers valuable conceptual approaches to follow in their quest for the most suitable vectors to turn mitochondrial gene therapy clinically feasible. Future studies should consider the optimization of mitochondrial genes' encapsulation, targeting ability, and transfection to mitochondria. Expectedly, this effort will bring bright results, contributing to important hallmarks in mitochondrial gene therapy.
线粒体是具有高度相关性的膜结合细胞器，负责细胞大多数生化反应中所使用的化学能量的产生。线粒体拥有自己的基因组，即线粒体DNA（mtDNA）。该基因组仅从母亲那里遗传而来，极易发生突变，主要是因为缺乏有效的修复系统。mtDNA突变与内分泌、代谢、神经退行性疾病甚至癌症有关。目前，治疗方法是基于使用一组药物来缓解患有线粒体疾病的患者的症状。线粒体基因治疗作为一种有前景的策略出现，因为它深入关注线粒体疾病的病因。开发合适的基于mtDNA的递送系统以靶向和转染哺乳动物线粒体是一个令人兴奋的研究领域，这在恢复线粒体正常功能这一具有挑战性的任务中取得了进展。本综述收集了有关此类纳米系统的组成、靶向性能或释放概况的相关知识，为研究人员在寻求最合适的载体以使线粒体基因治疗在临床上可行的过程中提供了有价值的概念方法。未来的研究应考虑优化线粒体基因的封装、靶向能力以及对线粒体的转染。可以预期，这一努力将带来丰硕成果，为线粒体基因治疗的重要里程碑做出贡献。
