Theoretically the position effect of the LNA substitutions could simply be explained by differences in thermodynamic stability of the resulting mRNA/oligonucleotide duplexes. To investigate this possibility we carried out Table 1 . The T m of the 18RNA/RNA18 duplex was the highest with 82 C in agreement with its high frameshifting efficiency. The 18RNA/DNA18 duplex had a much lower T m of 72 C, which is expected for an RNA/DNA hybrid, and also agreed with the lower frameshifting efficiency. The LNA substituted oligonucleotides, all had higher T m s (+4 to +9 C) than DNA18. The T m of L2-2 was with 81 C almost as high as that of RNA18.