Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Mitochondrion. 2019 Nov;49:178-188. doi: 10.1016/j.mito.2019.08.004. Epub 2019 Aug 28.
Mitochondrial gene therapy will be needed to treat mitochondrial diseases. We previously demonstrated mitochondrial gene silencing by the mitochondrial delivery of antisense RNA oligonucleotide (ASO) targeting mtDNA-encoded mRNA using a MITO-Porter, a liposomal nano carrier system designed for mitochondrial delivery. Here, we report on the efficient packaging of ASO in the MITO-Porter via a nanoparticle packaging method, which showed a 10-fold higher packaging efficiency than the conventional method. The constructed carrier showed a decrease in the target mRNA levels and ATP production. These results indicate that such a MITO-Porter has potential for use in therapies designed to regulate mitochondrial function.
线粒体基因治疗将需要治疗线粒体疾病。我们之前使用靶向 mtDNA 编码 mRNA 的线粒体递送反义 RNA 寡核苷酸 (ASO) 通过 MITO-Porter 实现了线粒体基因沉默，MITO-Porter 是一种专为线粒体递送来设计的脂质体纳米载体系统。在这里，我们报告了通过纳米颗粒包装方法将 ASO 高效包装到 MITO-Porter 中的情况，与传统方法相比，该方法的包装效率提高了 10 倍。构建的载体显示靶 mRNA 水平和 ATP 产生降低。这些结果表明，这种 MITO-Porter 具有用于调节线粒体功能的治疗的潜力。
