Vol. 5 No. 1 (2021)
Feature Articles

History of Research on Antisense Oligonucleotide Analogs

Jack S. Cohen
Chemistry Department, Ben Gurion University, Be’er Sheva, Israel

Published 2021-03-01


  • Antisense,
  • Oligonucleotide,
  • Analogs,
  • Therapeutic,
  • RNA

How to Cite

Cohen, J. S. (2021). History of Research on Antisense Oligonucleotide Analogs. Substantia, 5(1). https://doi.org/10.36253/Substantia-964


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.


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  5. It should be mentioned that there was a prior publication that termed the antisense approach “complementarily addressed” from a group in the USSR, in which they used hexanucleotides attached to reactive groups to bind to and modify specific sites in tRNA. See section on covalently linked nucleic acids.
  6. I use the term "oligo" to mean any oligonucleotide and ASO to refer to an antisense oligonucleotide
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  10. I published a fictionalized account of my experiences in my book "Antisense" in 2014.
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