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.