Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
J Control Release. 2013 Dec 28;172(3):805-11. doi: 10.1016/j.jconrel.2013.09.029. Epub 2013 Oct 4.
Mitochondrial genetic disorders are a major cause of mitochondrial diseases. It is therefore likely that mitochondrial gene therapy will be useful for the treatment of such diseases. Here, we report on the possibility of mitochondrial gene delivery in skeletal muscle using hydrodynamic limb vein (HLV) injection. The HLV injection procedure, a useful method for transgene expression in skeletal muscle, involves the rapid injection of a large volume of naked plasmid DNA (pDNA) into the distal vein of a limb. We hypothesized that the technique could be used to deliver pDNA not only to nuclei but also to mitochondria, since cytosolic pDNA that is internalized by the method may be able to overcome mitochondrial membrane. We determined if pDNA could be delivered to myofibrillar mitochondria by HLV injection by PCR analysis. Mitochondrial toxicity assays showed that the HLV injection had no influence on mitochondrial function. These findings indicate that HLV injection promises to be a useful technique for in vivo mitochondrial gene delivery.
线粒体遗传疾病是线粒体疾病的主要原因。因此，线粒体基因治疗很可能对这类疾病的治疗有用。在这里，我们报告了使用水力肢体静脉（HLV）注射将线粒体基因递送到骨骼肌中的可能性。HLV 注射程序是一种在骨骼肌中表达转基因的有效方法，涉及将大量的裸露质粒 DNA（pDNA）快速注入肢体的远端静脉。我们假设该技术不仅可以将 pDNA 递送到细胞核，还可以递送到线粒体，因为该方法内化的细胞质 pDNA 可能能够克服线粒体膜。我们通过 PCR 分析确定 HLV 注射是否可以将 pDNA 递送到肌原纤维线粒体。线粒体毒性测定表明，HLV 注射对线粒体功能没有影响。这些发现表明，HLV 注射有望成为一种有用的体内线粒体基因传递技术。
