新型阳离子类胡萝卜素脂质作为反义寡核苷酸传递载体在杜氏肌营养不良症外显子跳跃中的应用。

Novel cationic carotenoid lipids as delivery vectors of antisense oligonucleotides for exon skipping in Duchenne muscular dystrophy.

机构信息

School of Biological Sciences, Royal Holloway-University of London, Egham, Surrey TW20 0EX, UK.

出版信息

Molecules. 2012 Jan 24;17(2):1138-48. doi: 10.3390/molecules17021138.

Duchenne Muscular Dystrophy (DMD) is a common, inherited, incurable, fatal muscle wasting disease caused by deletions that disrupt the reading frame of the DMD gene such that no functional dystrophin protein is produced. Antisense oligonucleotide (AO)-directed exon skipping restores the reading frame of the DMD gene, and truncated, yet functional dystrophin protein is expressed. The aim of this study was to assess the efficiency of two novel rigid, cationic carotenoid lipids, C30-20 and C20-20, in the delivery of a phosphorodiamidate morpholino (PMO) AO, specifically designed for the targeted skipping of exon 45 of DMD mRNA in normal human skeletal muscle primary cells (hSkMCs). The cationic carotenoid lipid/PMO-AO lipoplexes yielded significant exon 45 skipping relative to a known commercial lipid, 1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine (EPC).

杜氏肌营养不良症（DMD）是一种常见的遗传性、不可治愈的致命性肌肉萎缩疾病，由缺失导致 DMD 基因的阅读框中断，从而无法产生功能性肌营养不良蛋白。反义寡核苷酸（AO）靶向外显子跳跃恢复了 DMD 基因的阅读框，表达了截断但仍具有功能的肌营养不良蛋白。本研究旨在评估两种新型刚性阳离子类胡萝卜素脂质 C30-20 和 C20-20 在递送针对正常人类骨骼肌原代细胞（hSkMCs）中 DMD mRNA 第 45 外显子靶向跳跃的磷酰胺吗啉代寡核苷酸（PMO）AO 方面的效率。与已知的商业脂质 1,2-二肉豆蔻酰基-sn-甘油-3-乙基磷酸胆碱（EPC）相比，阳离子类胡萝卜素脂质/PMO-AO 脂质体产生了显著的第 45 外显子跳跃。