LAUSR

We analyzed the effect of modified nucleotides within gapmer antisense oligonucleotides on RNase H mediated gene silencing. Additionally, short hairpins were introduced into antisense oligonucleotides as structural motifs, and their influence on biological and physicochemical properties of pre‐structured gapmers was investigated for the first time. The results indicate that two LNA residues in specified positions of the gap flanking regions are sufficient and favorable for efficient knock‐down of the β‐actin gene. Furthermore, the introduction of other modified nucleotides, i. e. glycyl‐amino‐LNA−T, 2′‐O‐propagyluridine, polyamine functionalized uridine, and UNA, in specified positions, also increases the inhibition of β‐actin expression. Importantly, the presence of hairpins within the gapmers improves their silencing properties.