History of Research on Antisense Oligonucleotide Analogs

Abstract

In the search for novel therapeutics, antisense oligonucleotide (ASO) analogs have been a major focus of research for over 40 years.  They use the antisense strategy, namely they have a nucleic acid base sequence that is complementary to a portion of a specific mRNA that is produced in the cell, or to a viral RNA, in order to selectively inhibit gene expression. Oligonucleotides need to be chemically modified to stabilize them against hydrolysis by endogenous nucleases. Until now several phosphorothioate (PS) oligonucleotide analogs have been approved by the FDA for human use. This article seeks to provide a history of this subject to date.