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.
CITATION STYLE
Hara, R. I., Yoshioka, K., & Yokota, T. (2020). DNA–RNA heteroduplex oligonucleotide for highly efficient gene silencing. In Methods in Molecular Biology (Vol. 2176, pp. 113–119). Humana Press Inc. https://doi.org/10.1007/978-1-0716-0771-8_8
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