Identification of sequence motifs in oligonucleotides whose presence is correlated with antisense activity

Design of antisense oligonucleotides targeting any mRNA can be much more ef ficient when several activity-enhancing motifs are included and activity-de creasing motifs are avoided, This conclusion was made after statistical ana lysis of data collected from >1000 experiments with phosphorothioate-modifi ed oligonucleotides. Highly significant positive correlation between the pr esence of motifs CCAC, TCCC, ACTC, GCCA and CTCT in the oligonucleotide and its antisense efficiency was demonstrated, In addition, negative correlati on was revealed for the motifs GGGG, ACTG, AAA and TAA, It was found that t he likelihood of activity of an oligonucleotide against a desired mRNA targ et is sequence motif content dependent.