ArticleMethods in molecular biology (Clifton, N.J.)2026
DNA/RNA Heteroduplex Oligonucleotide for Highly Efficient Gene Silencing.
Article in Methods in molecular biology (Clifton, N.J.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Heteroduplex oligonucleotides (HDOs) are a novel type of oligonucleotide drugs based on the hybrid duplex between an antisense oligonucleotide (ASO) strand and its complementary RNA (cRNA) strand. HDOs were originally designed to enhance the pharmacokinetic properties of RNase H-dependent ASOs that carry ligand molecules on the cRNA strand. The first HDOs conjugated with α-tocopherol (toc-HDOs) demonstrated efficient silencing in various tissues and cells, including liver, endothelial cells in the brain, peripheral nerve, and immune cells. Cholesterol-conjugated HDOs (chol-HDOs) were shown to be efficiently delivered to the brain and to induce knockdown in brain cells. Furthermore, the HDO technology was found to be applicable to more than just gapmer-type oligonucleotides. The silencing efficiency of ASO-antimiRs based on LNA/DNA mixmers was improved, as were the pharmacokinetics of splicing-modulating PMOs by combining HDO formation with cholesterol. Therefore, HDO technology has been demonstrated to be a versatile platform for developing effective oligonucleotide therapeutics.
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