Liquid-Phase Synthesis of Oligonucleotides

  • Satoshi KatayamaEmail author
  • Kunihiro Hirai


This review will summarize recent progress of liquid-phase oligonucleotide synthesis and also briefly introduce the challenge to develop a process that applies our original liquid-phase synthesis technology for practical use.

Recent progress in various types of oligonucleotide therapeutics, such as antisense, aptamer, siRNA and miRNA, has led to growing demand for economical and/or large scale production. Conventionally-known solid-phase synthesis which has been only a method of choice over the past few decades rapidly supplies oligonucleotides in high quality but in a limited quantity. Major issues of solid-phase synthesis that need to be addressed are scale-up and manufacturing cost. The former is attributable to the dedicated synthesizer’s capacity and the latter associate with heterogeneous reactions: use of expensive resins and excess amidite reagents.

Liquid-phase approaches may overcome these limitations. Behind the progress of solid-phase synthesis, researchers have investigated unique liquid-phase approaches. Among them, several methods utilizing soluble supports instead of solid resins are combining the advantage of solid-phase synthesis and liquid-phase synthesis, and expected to have possibility of industry applicable methods.


Liquid-phase oligonucleotide synthesis Solution-phase Large scale production Soluble supports Scale-up AJIPHASE® 


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© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Bio-Functional Molecular Chemistry GroupResearch Institute for Bioscience Products & Fine Chemicals, Ajinomoto Co. Inc.Kawasaki-ku, Kawasaki-shiJapan

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