Issue: May / June 2023

Nucleic acid-based therapeutics, have seen increased activity in the development of treatments for rare diseases due to the possibility of rational design and their shorter and cost-effective development cycles. Since the first approvals new compound approvals are occurring annually, and massive growth is expected over the next few years. The elimination of many barriers has contributed to their success. However, it is necessary to conquer new tissues to bring novel therapies to the market. The world’s production capacities are already full with the most advanced products in development and those on the market. To adapt to the market, the industry will have to deal with innovative production and sustainability constraints, which calls for the creation of cutting-edge strategies and processes.

The number of approved nucleic acid drugs has increased recently owing to progress in the medicinal chemistry of oligonucleotide therapeutics; the expansion of drug sales is providing new API demand opportunities for CDMO. Nucleic acid drugs utilize various chemically modified nucleotides, to avoid decomposition by nucleases in the human body and improve the RNA binding affinity. The production of modified nucleotides requires organic synthesis technology and sufficient production capacity at CDMO. This study focuses on the synthetic process of modified nucleotides, especially those comprising bridged nucleic acids (BNAs), and explains the progress in BNA research from a process chemistry perspective.