Therapeutic implications of antisense oligonucleotides

Summary Antisense oligonucleotides and their derivatives have been shown to be specific inhibitors of gene expression. They are considered a very promising new generation of drugs, potentially useful in most human diseases, including cancers and viral infections. The elegance of the antisense oligonucleotides lies in their ability to bind, via standard Watson-Crick base pairing, a complementary region within a target mRNA. Although easily synthesized, therapeutic applications have been restricted by a number of difficulties including: stability, pharmacokinetic behavior (both a cellular and at systemic level), and the high cost of industrial production. The object of this review is to briefly describe the major properties of antisense oligonucleotides, the modalities currently under investigation to circumvent the difficulties in their use, and the up-to-date experimental applications, including findings from our own laboratory. As very few oligonucleotides need to be synthesized in order to obtain an active compound, compared with an average of 10000 new standard compounds, prospects are extremely exciting and worthy of maximum attention.