中文摘要：

目的：通过对反义寡核苷酸2′-O-甲氧乙基（2′-O-MOE）化学结构的体外实验,为杜兴肌肉萎缩症基因治疗方法提供一种候选的反义寡核苷酸药物。方法：在杜兴肌肉萎缩症小鼠H2K mdx细胞上转染不同长度和骨架修饰的2′-O-MOE反义寡核苷酸,利用RT-PCR技术检测其诱导外显子跳读的情况。结果：3种2′-O-MOE修饰的反义寡核苷酸体外诱导外显子跳读的效率显著高于目前临床检测的药物2′OmePS,表现出一定的浓度效应和时间效应。并且MOE25（PS）诱导外显子跳读的效率最好。结论：2′-O-MOE修饰的反义寡核苷酸能够有效地诱导H2K mdx细胞外显子跳读。

英文摘要：

Objective： To study a new antisense oligonucleotide （AO） chemistry- 2＇-O-Methoxyethyl （2＇-O-MOE） in a Duchenne muscular dystrophy （DMD）cellular model- H2K mdx cell and wish to provide a candidate antisense oligonucleotide drug for treating DMD. Methods： RT-PCR was utilized for detecting the exon skipping efficiency after in vitro transfection with different lengths and dif- ferent backbone modifications of 2＇-O-MOE AOs in HEK mdx cells. Results： Three tested 2＇-O-MOE modified AOs showed significant- ly higher level of exon skipping than that of 2＇ OmePS, which was used in current clinical trials. These 2＇-O-MOE modified AOs showed dose-dependent effect and timecourse effect. Among three 2＇-O-MOE modified AOs, MOE25（PS） was the best. Conclusion： It is shown that 2＇-O-MOE modified AOs are effective in inducing exon skipping in vitro.