Fig. 1. Chemistry of FDA-approved oligonucleotide drugs.

Chemical composition of the FDA-approved oligonucleotide drugs fomivirsen (part a), mipomersen (part b), inotersen (part c), eteplirsen (part d), golodirsen (part e), nusinersen (part f), patisiran (part g), givosiran (part h) and pegaptanib (part i). Drugs are ordered by mechanism of action. Drug names, trade names, principal developing company, modality and RNA target are described in Table 1 for each compound. The drug defibrotide consists of a mixture of single-stranded and double-stranded ribonucleotides of variable length and sequence composition harvested from pig intestine. It therefore cannot be easily represented in the same manner as the other oligonucleotide drugs and so is not shown here. GalNAc, N-acetylgalactosamine; PEG, polyethylene glycol; PMO, phosphorodiamidate morpholino oligonucleotide. Part i structure adapted from ref.²⁸⁴, Springer Nature Limited.