ANTISENSE OLIGODESOXYNUCLEOTIDE STRATEGIES IN RENAL AND CARDIOVASCULAR-DISEASE

Antisense oligodesoxynucleoties (ODN) provide a novel strategy to inhi bit RNA transcription and thereby the synthesis of the gene product. B ecause antisense ODN hybridize with the mRNA strand, they are highly s pecific. Their backbone structure has been modified to phosphorothioat es or phosphoamidates so that they can better withstand degradation af ter delivery. We have shown that antisense ODN are a useful research t ool to elucidate intracellular processes. The example we provide invol ves the inhibition of PKC signaling. Furthermore, we have shown the po tential clinical utility of antisense treatment. We successfully inhib ited the expression of the surface adhesion molecule ICAM-1 with antis ense ODN in a model of reperfusion injury. This model is highly applic able to the problem of delayed graft function in humans. However, ''ge tting there'' is a major problem and clearly less than half the fun. C ationic substances such as lipofectin have worked sufficiently well in the experimental setting. Viral gene transfer offers a possibility; h owever, viruses produce an additional series of problems. Liposomes ma y not provide sufficient transfer efficiency. Coating liposomes with v iral fusion proteins may offer an ideal way with which to deliver the goods into the cytoplasm of the target cell.