Novel bicyclo nucleosides, 2′- O,4′- C-ethylene nucleosides and 2′- O,4′- C-propylene nucleosides, were synthesized as building blocks for antisense oligonucleotides to further optimize the 2′- O,4′- C-methylene-linkage of bridged nucleic acids (2′,4′-BNA) or locked nucleic acids (LNA). Both the 2′- O,4′- C-ethylene- and propylene-linkage within these nucleosides restrict the sugar puckering to the N-conformation of RNA as do 2′,4′-BNA/LNA. Furthermore, ethylene-bridged nucleic acids (ENA) having 2′- O,4′- C-ethylene nucleosides had considerably increased the affinity to complementary RNA, and were as high as that of 2′,4′-BNA/LNA (Δ T m=+3∼5 °C per modification). On the other hand, addition of 2′- O,4′- C-propylene modifications in oligonucleotides led to a decrease in the affinity to complementary RNA. As for the stability against nucleases, incorporation of one 2′- O,4′- C-ethylene or one 2′- O,4′- C-propylene nucleoside into oligonucleotides considerably increased their resistance against exonucleases to an extent greater than 2′,4′-BNA/LNA. These results indicate that ENA is more suitable as an antisense oligonucleotide and is expected to have better antisense activity than 2′,4′-BNA/LNA.