In 1998, the US Food and Drug Administration (FDA) approved fomivirsen as the first therapeutic oligonucleotide therapeutic. This approval marked a revolution of mechanism of action discovered decades before finally coming to fruition. Since then, the landscape of chemical modifications of oligonucleotides, conjugations and formulations has evolved tremendously, contributing to improvements in stability, efficacy and safety. Today, more than a dozen antisense oligonucleotides (ASOs) and small interfering RNA (siRNA) drugs are on the market, most of which are designated as orphan drugs for treating rare genetic diseases.
