Yoshioka Kotaro, Kuwahara Hiroya, Nishina Kazutaka, Nagata Tetsuya, Yokota Takanori
Nihon Rinsho. 2015 Jun;73(6):1057-65.
Remarkable progress has been made in chemical modification and nonviral delivery systems that improve the properties and efficacy of therapeutics oligonucleotides therapeutics, such as antisense oligonucleotide (ASO) and small interfering RNA(siRNA). ASOs act through various mechanisms including the degradation of mRNA by RNase H (gapmer-type ASO) and the modulation alternative splicing patterns(splice switching oligonucleotide). Recent favorable outcomes in clinical trials for cancers and genetic diseases such as familial amyloid polyneuropathy and Duchenne muscular dystrophy indicate high clinical potency of oligonucleotide therapeutics. Here we reviewed recent advances in basic properties and clinical applications of ASO and siRNA, and provide future perspective on oligonucleotide therapeutics.
在化学修饰和非病毒递送系统方面已经取得了显著进展，这些进展改善了治疗性寡核苷酸（如反义寡核苷酸（ASO）和小干扰RNA（siRNA））的性质和功效。ASO通过多种机制发挥作用，包括通过RNase H降解mRNA（间隙mer型ASO）和调节可变剪接模式（剪接转换寡核苷酸）。最近在癌症和遗传性疾病（如家族性淀粉样多神经病和杜氏肌营养不良症）的临床试验中取得的良好结果表明寡核苷酸疗法具有很高的临床效力。在这里，我们综述了ASO和siRNA的基本特性和临床应用的最新进展，并对寡核苷酸疗法提供了未来展望。
