The expression of a gene can be selectively inhibited by antisense oligonucleotides (AOs) targeting the mRNA. However, if the target site in the mRNA is picked randomly, typically 20% or less of the AOs are effective inhibitors in vivo. The sequence properties that make an AO effective are not well understood, thus many AOs need to be tested to find good inhibitors, which is time consuming and costly. So far computational models have been based exclusively on RNA structure prediction or motif searches while ignoring information from other aspects of AO design into the model.