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Meunier, L ; Monsigny, M ; Roche, AC

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

Antisense & Nucleic Acid Drug Development 11 (2) 117-123

par Administrateur - publié le , mis à jour le

Abstract :

Oligodeoxynucleotides (ODN) are used largely as either primers, antisense, or tripler-forming units. Phosphodiester ODN (PO-ODN), which are very rapidly degraded by exonucleases, must be protected at their ends. Even so, their life span inside cells is quite short. Phosphorothioate ODN (PS-ODN) are less sensitive to nucleases and are extensively used as antisense, Unfortunately, unlike PO-ODN, they interact with a number of molecules, including proteins, in addition to their specific nucleic acid targets, Their affinity for their target is lower than that of PO-ODN, PS-ODN containing propyne groups 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 are not efficient when they are used as lipoplexes, but they act as specific antisense on electroporation.