DNA–RNA Heteroduplex Oligonucleotide for Highly Efficient Gene Silencing

Heteroduplex oligonucleotides (HDOs)Heteroduplex oligonucleotides (HDOs) were a novel type of nucleic acid drugs based on an antisenseAntisense oligonucleotide (ASO) strand and its complementary RNARNA (cRNA Complementary RNA strand (cRNA) ) strand. HDOs Heteroduplex oligonucleotides (HDOs) were originally designed to improve the properties of RNase H-dependent ASOs and we reported in our first paper that HDOs Heteroduplex oligonucleotides (HDOs) conjugated with an α-tocopherol ligand Ligands (Toc-HDO Alpha-tocopherol ligand (Toc-HDO) ) based on a gapmer Gapmers ASO showed 20 times higher silencing effect to liver Livers apolipoprotein B (apoB)Apolipoprotein B (ApoB) mRNA mRNAs in vivoIn 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.