Current status of development of oligonucleotide therapeutics

Abstract

Oligonucleotide therapeutics are single- or double-stranded DNA or RNA-based molecules consisting of short strand of nucleotides (generally 10-50 nucleotides). They are manufactured by chemical synthesis and act directly on RNA or protein. In recent years, oligonucleotide therapeutics, such as antisense oligonucleotides (ASOs), siRNAs, miRNAs, aptamers or CpG-motif oligodeoxynucleotides (CpG ODN), are active areas of drug development designed to treat a variety of genetic and/or intractable diseases. So far, eight oligonucleotide therapeutics have achieved marketing authorization in USA or Europe, i.e. fomivirsen (Vitravene®), pegaptanib (Macugen®), mipomersen (Kynamro®), eteplirsen (Exondys 51®), nusinersen (Spinraza®), inotersen (Tegsedi®), patisiran (Onpattro®), and hepatitis B vaccine containing CpG ODN (CpG1018) as adjuvants (HEPLISAV-B®), and more than 150 oligonucleotide therapeutics are currently in clinical development. In this review, I outline classification, modifications and mechanism of actions of oligonucleotide therapeutics, and introduce the current status of development of RNA-targeted oligonucleotide therapeutics (ASOs, siRNAs and miRNAs).