Design and synthesis of oatp subtype-specific antisense oligonucleotides having 2'-O,4'-C-ethylene-bridged nucleic acids (ENA).

To select antisense oligonucleotides (AONs) that specifically target the genes of rat organic anion transporting polypeptide (oatp) subtypes, in vitro selection and an alignment program were used. When we incorporated a couple of our original 2'-O,4'-C-ethylene nucleoside (ENA) residues into the AONs at both the 3' and 5' ends, the inhibitory activity of these oatp subtype-specific AONs was enhanced. This strategy of combining in vitro selection with the use of an alignment program as well as incorporating ENA residues, was effective in synthesizing oatp subtype-specific AONs.