Research and development of oligonucleotide therapeutics in Japan for rare diseases

Inherited gene mutations, insertions, deletions of single genes cause most of the rare diseases. Oligonucleotide therapeutics represent one of the most flexible platforms for developing drugs for rare diseases. Presently, 15 oligonucleotide therapeutics have been approved in the United States of America (USA) to treat various rare diseases and 4 oligonucleotide therapeutics (eteplirsen, golodirsen, viltolarsen and casimersen) are used to treat Duchenne muscular dystrophy. The progress of oligonucleotide therapeutics in Japan has emerged from several decades of basic research. In March 2020, viltolarsen, developed by Japanese companies, was approved as a treatment for Duchenne muscular dystrophy. This article discusses the research and development of oligonucleotide therapeutics for rare diseases from the viewpoint of the proprietary technologies in Japanese pharmaceutical and bio-venture companies. Recently, oligonucleotide therapeutics have received awareness following small molecule and antibody drugs. The research related to oligonucleotide therapeutics in Japan is based on the results of basic research accumulated over several decades. For example, viltolarsen (NS-065/NCNP-01) from Nippon Shinyaku was approved for Duchenne muscular dystrophy in Japan and USA in 2020. Here, we report the development of oligonucleotide therapeutics and the role of Japan.