Propynylated phosphodiester oligonucleotides inhibit ICAM-1 expression in A549 cells on electroporation

Oligodeoxynucleotides (ODN) are used largely as either primers, antisense, or tripler-forming units. Phosphodiester ODN (PO-ODN), which are very rapid ly degraded by exonucleases, must be protected at their ends. Even so, thei r life span inside cells is quite short. Phosphorothioate ODN (PS-ODN) are less sensitive to nucleases and are extensively used as antisense, Unfortun ately, unlike PO-ODN, they interact with a number of molecules, including p roteins, in addition to their specific nucleic acid targets, Their affinity for their target is lower than that of PO-ODN, PS-ODN containing propyne g roups on C5 of pyrimidine have been shown to have a higher affinity toward their nucleic acid target. Here, we show that propynylated PO-ODN are more stable and much more efficient than their propyne-free counterparts. They a re not efficient when they are used as lipoplexes, but they act as specific antisense on electroporation.