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Liquid-Phase Synthesis of Oligonucleotides

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Synthesis of Therapeutic Oligonucleotides

Abstract

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.

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Authors and Affiliations

  1. Bio-Functional Molecular Chemistry Group, Research Institute for Bioscience Products & Fine Chemicals, Ajinomoto Co. Inc., Kawasaki-ku, Kawasaki-shi, Japan

    Satoshi Katayama & Kunihiro Hirai

Authors
  1. Satoshi Katayama
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  2. Kunihiro Hirai
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Correspondence to Satoshi Katayama .

Editor information

Editors and Affiliations

  1. Osaka University, Suita, Osaka, Japan

    Satoshi Obika

  2. Tokyo Institute of Technology, Yokohama, Kanagawa, Japan

    Mitsuo Sekine

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Katayama, S., Hirai, K. (2018). Liquid-Phase Synthesis of Oligonucleotides. In: Obika, S., Sekine, M. (eds) Synthesis of Therapeutic Oligonucleotides. Springer, Singapore. https://doi.org/10.1007/978-981-13-1912-9_5

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