DNA传递的细胞内靶点:细胞核和线粒体。

Vladimir P Torchilin, Ban-An Khaw, Volkmar Weissig
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引用次数: 29

摘要

所有关于细胞内DNA传递的讨论都基于一个看似显而易见的假设,即关键任务是将完整的DNA带入细胞质室,然后DNA将找到合适的位置。核基因组通常被认为是这个“正确的地方”。然而,直到最近,在大量关于细胞内DNA传递的实验中,人们几乎完全忽略了细胞含有另一种基因组,即线粒体基因组。而且,在许多情况下,这个基因组应该成为一个治疗目标。在细胞内传递时,DNA实际上有两条路径——通往细胞核和线粒体,在这两条路径之间的正确选择可能对基因治疗的成功至关重要。当然,核DNA传递要比线粒体传递先进得多。此外,来自细胞质的游离DNA有很强的自发结合核基因组的倾向。线粒体作为DNA的靶点,其可达性要低得多,但仍是一个重要的可达位点。虽然DNA的核传递正在积极研究中,只是等待更好的方案来阐述,但实际适用的线粒体DNA传递还处于早期阶段,必须从头开始开发。在我们对细胞内DNA传递的研究中,我们试图开发靶向DNA到细胞核和线粒体的新方案。在本章中,我们将简要描述我们最近在这两个重要领域的实验。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Intracellular targets for DNA delivery: nuclei and mitochondria.

All discussions on the intracellular delivery of DNA are based on a seemingly evident assumption that the key task is to bring the intact DNA into the cell cytoplasmic compartment, and then the DNA will find its way to a right place. The nuclear genome is usually considered to be this "right place." However, until recently, in numerous experiments on the intracellular DNA delivery, it has been almost completely neglected that cells contain another genome, the mitochondrial one. And, in many cases, this genome should become a therapeutic target. Being delivered inside the cell, DNA actually has two ways to go--to nuclei and to mitchondria, and the proper choice between these two ways may be decisive for the success of gene therapy. Certainly, nuclear DNA delivery is far more advanced than mitochondrial delivery one. In addition, free DNA from the cytoplasm has a strong tendency to spontaneously associate with the nuclear genome. Mitochondria as a target for DNA have much less accessibility, still remaining an important site to reach. Whereas the nuclear delivery of DNA is under active investigation and just awaits better protocols to be elaborated, practically applicable mitochondrial DNA delivery is at its early stage and must be developed almost from scratch. In our studies on intracellular DNA delivery, we have attempted to develop new protocols for targeting DNA to nuclei and to mitochondria. In this chapter we provide a brief description of our recent experiments in both of these important areas.

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