Efficient Methods for Selecting Sirna Sequences by Using the Average Silencing Probability and a Hidden Markov Model

Short interfering RNA (siRNA) has been widely used for studying gene functions in mammalian cells but varies markedly in its gene silencing efficacy. Although many design rules/guidelines for effective siRNAs based on various criteria have been reported recently, there are only a few consistencies among them. This makes it difficult to select effective siRNA sequences in mammalian genes. This paper first clarifies problems of the recently reported siRNA design guidelines and then proposes a new method for selecting effective siRNA sequences from many possible candidates by using the average silencing probability on the basis of large number of known effective siRNAs. It is different from the previous score-based siRNA design techniques and can predict the probability that a candidate siRNA sequence will be effective. The results of evaluating it by applying it to recently report effective and ineffective siRNA sequences for various genes indicate that it would be useful for many other genes. The evaluation results indicate that the proposed method would be useful for many other genes. It should therefore be useful for selecting siRNA sequences effective for mammalian genes. The paper also describes another method using a Hidden Markov Model (HMM) to select the optimal functional siRNAs.