Prediction of antisense oligonucleotide binding affinity and activity in cell culture

The authors have developed a method that uses RNA secondary structure prediction and an appropriate thermodynamic cycle to predict the free energy of hybridization between an antisense oligonucleotide and its target mRNA. They applied this method to determine, theoretically, the oligonucleotides which bind most strongly to the rabbit β-globin (RBG) mRNA, for which a large experimental data set is available. The model accurately predicts the trend in binding affinity and, more importantly, identifies the highest binding affinity sequences quite accurately (six out of the highest ten). Recent data indicate that the method also yields sequences that inhibit the production of the gp130 cytokine signaling protein in the H35 rat hepatoma cell line