Abstract
Oligonucleotide therapeutics, represented by antisense and siRNA, are designed to bind to RNA by Watson-Crick base pairing. They are attracting attention as a new modality for treating diseases, especially hereditary and intractable diseases that have been difficult to treat in the past. The first two nucleic acid drugs on the market were both topically administered within the eye, followed by the first systemically administered oligonucleotide drug in 2013. Efficient delivery to target organs or cellwas one challenge. siRNA conjugated with N-acetylgalactosamine（GalNac）, which binds to a ligand on hepatocytes（ASGPR）, was developed and its usefulness was demonstrated in clinical trials. Now, four GalNac-siRNAs are on the market by 2022. The development of ligand-binding oligonucleotide drugs especially extra-hepatic target is expected to advance further in the future. Here, we review the current status of oligonucleotidedrug development, with a particular focus on ligand-directed development.
