Design and Synthesis of Protecting Groups for Pro-oligo Type Nucleic Acid-based Drugs

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  • Saneyoshi Hisao
    Department of Chemistry, Shiga University of Medical Science
  • Ono Akira
    Department of Material and Life Chemistry, Kanagawa University

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  • プロオリゴ型核酸医薬を志向した保護基の開発研究
  • プロオリゴガタ カクサン イヤク オ シコウ シタ ホゴキ ノ カイハツ ケンキュウ

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Abstract

<p>Oligonucleotide-based therapeutics, such as antisense oligonucleotides and small interfering RNAs(siRNAs), are fast emerging as the next generation of chemotherapeutics. However, a major issue for oligonucleotide-based therapeutics involves effective intracellular delivery of the active molecules into the cells. Several methods such as lipid nanoparticle encapsulation and conjugation of functional molecules have been reported. As an alternative approach, the use of pro-oligonucleotides (pro-oligos) offers several advantages, including improved enzymatic stability, thereby avoiding the need for transfection reagents for the delivery of oligonucleotides into cells. We have developed several bio-labile protecting groups for the pro-oligos. This article describes the design and synthesis of bio-labile protecting groups and their application to pro-oligo type molecules for the development of oligonucleotide therapeutics.</p>

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