Short interfering RNA (siRNA) has become a major tool in basic sciences for functional gene knockdown and in molecular medicine to suppress aberrant gene expression. In natural system it is not always possible to get highly effective siRNA against a target. Thus it is important to design highly effective siRNA by making minimum mutation in it against a given target.
This study can be divided into two parts. In the first part we developed a support vector machine model for predicting siRNA efficacy on existing datasets. The performance of our model is as good as other well-known methods when tested on independent data. In the second part we developed a strategy where one can design mutant siRNA of desired efficacy. In this approach we mutated a given siRNA on all possible sites with all possible nucleotides. Efficacy of mutated siRNAs is predicted using SVM model. It is well known from literature that making mismatches between siRNA and target affect the silencing efficacy. Thus we have incorporated the rules derived from base mismatches experimental data to find out over all efficacy of mutated siRNAs. Finally we have developed this webserver, desiRm, which is freely accessible for academic user.
The server can be used for two purposes: (1) submit an mRNA to find out effective siRNAs against it, and (2) submit a siRNA and its target sequence to design more efficacious siRNAs by nucleotide mismatch. This study presents a novel method to make more potent siRNA against a target. This way it can be implemented to design effective siRNA against a unique target region but associated with very least efficacy. It will also help to designing of siRNA for disease isoform of heterozygous single nucleotide polymorphism gene without depleting the wild type protein.
The main aim of this server is to make more efficiaent siRNA against a target site using nucleotide mismatch approach.
Please click here to see Dr. Raghava's group
Please cite following paper, if you are using this server
Ahmed, F. and Raghava, G. P. S. (2011) Designing of Highly Effective Complementary and Mismatch siRNAs for Silencing a Gene Plos ONE 6(8): e23443
