In addition to RNA oligonucleotides, we demonstrated that LNA/DNA mix-mers are also capable of stimulating efficient À1 ribosomal frameshifting in contrast to DNA oligonucleotides. Replacing 2 nt in a DNA oligonucleotide by LNA was already sufficient to reach the same level of frameshifting as with a comparable RNA oligonucleotide. However, the excellent affinity of LNA oligonucleotides could be a double-edged sword in certain cases. In our experimental system, the oligonucleotides are partly self-complementary and this resulted in the formation of dimers ( Figure 5 ), which were apparently unable to induce frameshifting (LNA6, Figure 3 ). Hence, LNA substitutions should be optimized in a sequence that is prone to form dimers. In our SF462 construct (Figure 4) , the optimal number of LNA substitutions to induce the most significant amount of frameshifting is four. LD6 with two additional LNA substitutions did not improve the efficiency. Thus, our results suggest that the first 4 bp are critical for antisense-induced frameshifting. A likely explanation is that when a ribosome that is translating the slippery sequence, the helicase active site is around position +11, with respect to the first nucleotide of the P-site, which is close to the first base pair of the mRNA/ oligonucleotide duplex (35) . Increasing the local thermodynamic stability in this region may prevent ribosomes to unwind RNA structures, causing ribosomal pausing at the slippery sequence, and finally results in a higher frequency of ribosomal frameshifting.