The effects of single LNA substitutions at the 3 0 end of the 2 0 -O-methyl strand was studied in duplexes of the form, Table 1 ). If N is A, C or G, then LNA substitutions have similar effects. On average, an LNA substitution makes duplex stability more favorable by 1.2 kcal/mol at 37 C. In the two sequences with a 3 0 terminal LNA U on the 2 0 -O-methyl strand, duplex stability is, however, affected little, averaging a destabilization of 0.08 kcal/ mol at 37 C. In both cases, the terminal U is preceded by a GC pair, but both orientations of the GC pair give similar destabilization upon LNA substitution at the 3 0 terminal U.