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Kidney Int. 1998 Jun;53(6):1550-8.

Antisense oligodesoxynucleotide strategies in renal and cardiovascular disease.

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1
Franz Volhard Clinic, Max Delbrück Center for Molecular Medicine, Virchow Klinikum-Charité Humboldt University of Berlin, Germany. haller@mdc-berlin.de

Abstract

Antisense oligodesoxynucleotides (ODN) provide a novel strategy to inhibit RNA transcription and thereby the synthesis of the gene product. Because antisense ODN hybridize with the mRNA strand, they are highly specific. Their backbone structure has been modified to phosphorothioates or phosphoamidates so that they can better withstand degradation after delivery. We have shown that antisense ODN are a useful research tool to elucidate intracellular processes. The example we provide involves the inhibition of PKC signaling. Furthermore, we have shown the potential clinical utility of antisense treatment. We successfully inhibited the expression of the surface adhesion molecule ICAM-1 with antisense ODN in a model of reperfusion injury. This model is highly applicable to the problem of delayed graft function in humans. However, "getting there" is a major problem and clearly less than half the fun. Cationic substances such as lipofectin have worked sufficiently well in the experimental setting. Viral gene transfer offers a possibility; however, viruses produce an additional series of problems. Liposomes may not provide sufficient transfer efficiency. Coating liposomes with viral fusion proteins may offer an ideal way with which to deliver the goods into the cytoplasm of the target cell.

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