Recent advances in scale-up of modified oligodeoxynucleotides

Progress in the field of oligonucleotide therapeutics has created the need for scale-up of oligonucleotide synthesis from milligram to multikilogram and higher. The synthesis and scale-up of modified oligonucleotides has undergone enormous progress in recent years. The synthesis of oligonucleotide phosphorothioates can be routinely carried out at scales of 10 to 100 mmol with a total cost of less than US$300 per gram. Further developments on increasing purity and reducing cost will rely on the invention of novel reagents and processes. The recent progress and challenges in scale-up of oligonucleotides are discussed herein.