Department of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Methods Mol Biol. 2020;2176:113-119. doi: 10.1007/978-1-0716-0771-8_8.
Heteroduplex oligonucleotides (HDOs) were a novel type of nucleic acid drugs based on an antisense oligonucleotide (ASO) strand and its complementary RNA (cRNA ) strand. HDOs were originally designed to improve the properties of RNase H-dependent ASOs and we reported in our first paper that HDOs conjugated with an α-tocopherol ligand (Toc-HDO ) based on a gapmer ASO showed 20 times higher silencing effect to liver apolipoprotein B (apoB) mRNA in vivo than the parent ASO. Thereafter the HDO strategy was found to be also effective for improving the properties of ASOs modulating blood-brain barrier function and ASO antimiRs which are RNase H-independent ASOs. Therefore, the HDO strategy has been shown to be versatile technology platform to develop effective nucleic acid drugs.
异源双链寡核苷酸 (HDOs) 是一种新型的核酸药物，基于反义寡核苷酸 (ASO) 链及其互补 RNA (cRNA) 链。HDOs 最初被设计用于改善依赖 RNA 酶 H 的 ASO 的性质，我们在第一篇论文中报道，基于间隔寡核苷酸 ASO 的与 α-生育酚配体 (Toc-HDO) 缀合的 HDO 显示出比亲本 ASO 高 20 倍的体内肝脏载脂蛋白 B (apoB) mRNA 沉默效果。此后，人们发现 HDO 策略对于改善调节血脑屏障功能的 ASO 和不依赖 RNA 酶 H 的 ASO 抗 miRNA 的性质也有效。因此，HDO 策略已被证明是开发有效核酸药物的多功能技术平台。
