Figure 5. Mechanism of action of intercellular adhesion molecule 1 (ICAM-1) antisense oligonucleotides. Before entering cells, the ICAM-1 antisense oligonucleotides may be damaged by nucleases. Different chemical modifications (e.g. the attachment of phosphorothiate groups) prevent damage by nucleases. The negative charges on the antisense oligonucleotides facilitate their binding to the positively charged cell membranes. In the cytoplasm, ICAM-1 antisense oligonucleotides bind to the specific sequence on ICAM-1 messenger RNA (mRNA) molecules. The formation of oligonucleotide–mRNA duplexes activates the ribonuclease H (RNase H) enzyme, which cuts ICAM-1 mRNA, preventing the synthesis of ICAM-1 protein (fig005ssh).