Delivery of antisense oligonucleotides to the vascular wall

Antisense oligonucleotides are short segments of synthetic DNA designed to contain sequences of bases complementary to the DNA or RNA of a particular target gene of interest. By binding to the target, the antisense oligonucleotides can prevent translation of the gene into protein via different mechanisms including destruction of the AS-ODN-nucleic acid hybrid by RNAse H, steric hindrance of the ribosome causing interference of protein elongation, or blockage of the initiation of protein translation (1). Figure 1 shows the possible mechanisms of action of AS-ODNs. Fig. 1. Possible mechanisms of action of antisense oligonucleotides. 1, Aptameric or specific binding to transcription factors; 2, triplex formation via binding to doublestranded DNA resulting in steric inhibition of transcription of DNA into RNA; 3, specific binding to splice junctions or poly A signals inhibits mRNA maturation; 4, inhibition of transport from the nucleus; 5, specific binding to mRNA causing inhibition of translation via steric hindrance of ribosomal complexes; 6, duplex formation causing RNAse H mediated cleavage of mRNA; 7, aptameric binding to protein causing inhibition of protein function.