DNA-RNA 杂合寡核苷酸可高效基因沉默。

DNA-RNA Heteroduplex Oligonucleotide for Highly Efficient Gene Silencing.

机构信息

Department of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.

出版信息

Methods Mol Biol. 2020;2176:113-119. doi: 10.1007/978-1-0716-0771-8_8.

DOI:10.1007/978-1-0716-0771-8_8

PMID:32865786

Abstract

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.

摘要

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。