Negishi Yoichi, Endo-Takahashi Yoko, Ishiura Shoichi
Department of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan.
Department of Medical Life Systems, Faculty of Life and Medical Sciences, Doshisha University, Kyotanabe, Kyoto, Japan.
Methods Mol Biol. 2018;1828:481-487. doi: 10.1007/978-1-4939-8651-4_30.
Abnormal splicing of the chloride channel 1 (CLCN1) gene causes myotonic dystrophy type 1 (DM1). Therefore, controlling the alternative splicing process of this gene by antisense oligonucleotides can be a promising treatment for DM1. In this study, we describe an efficient phosphorodiamidate morpholino oligomer (PMO) delivery method by ultrasound-mediated bubble liposomes, which is a known gene delivery tool with ultrasound exposure, to treat skeletal muscles in a DM1 mouse model, HSA. Effective delivery of PMO using this technique can help control the alternative splicing of the Clcn1 gene via exon skipping and enhance the expression of Clcn1 protein in skeletal muscles and the amelioration of myotonia. Thus, exon skipping by PMO delivery with ultrasound-mediated BLs may be feasible in myotonic dystrophy model mice.
氯离子通道1（CLCN1）基因的异常剪接会导致1型强直性肌营养不良（DM1）。因此，通过反义寡核苷酸控制该基因的可变剪接过程可能是治疗DM1的一种有前景的方法。在本研究中，我们描述了一种通过超声介导的气泡脂质体实现有效磷酰二胺吗啉代寡聚物（PMO）递送的方法，超声介导的气泡脂质体是一种已知的经超声照射的基因递送工具，用于治疗DM1小鼠模型HSA中的骨骼肌。使用该技术有效递送PMO有助于通过外显子跳跃控制Clcn1基因的可变剪接，并增强骨骼肌中Clcn1蛋白的表达以及改善肌强直。因此，在强直性肌营养不良模型小鼠中，通过超声介导的气泡脂质体递送PMO进行外显子跳跃可能是可行的。
