Our data also showed that a single LNA modification is not sufficient to turn a DNA oligonucleotide into an efficient frameshift inducer but that a second LNA is needed. The best position for the second modification appeared to be also close to the 3 0 -end of the oligonucleotide. Although one could expect that spacing of two LNA groups by two non-modified sugars as applied in probes for miRNAs, results in the optimal induction of the 3 0 -endo conformation in the neighboring sugars (36), this was not the case in our frameshift assays. Here such a spacing was less efficient (see data for L2-4, Figure 6 ). However, we have not investigated if possible differences of self-dimerization behavior of these oligonucleotides accounts for the different stimulating activities, since such effects were only observed when six LNA modifications were introduced in an oligonucleotide of this sequence.