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Review
. 2023 Nov 17:14:1304342.
doi: 10.3389/fphar.2023.1304342. eCollection 2023.

Antisense oligonucleotides: a novel Frontier in pharmacological strategy

D Collotta #  1 , I Bertocchi #  1   2 , E Chiapello  1 , M Collino  1
Affiliations
Review

Antisense oligonucleotides: a novel Frontier in pharmacological strategy

D Collotta et al. Front Pharmacol. .

Abstract

Antisense oligonucleotides (ASOs) are short single stranded synthetic RNA or DNA molecules, whereas double-stranded RNA nucleotide sequences are called small interfering RNA (siRNA). ASOs bind to complementary nucleic acid sequences impacting the associated functions of the targeted nucleic acids. They represent an emerging class of drugs that, through a revolutionary mechanism of action, aim to directly regulate disease-causing genes and their variants, providing an alternative tool to traditional "protein-specific" therapies. The majority of the ASOs are designed to treat orphan genetic disorders that in most of the cases are seriously disabling and still lacking an adequate therapy. In order to translate ASOs into clinical success, constant technological advances have been instrumental in overcoming several pharmacological, toxicological and formulation limitations. Accordingly, chemical structures have been recently implemented and new bio-conjugation and nanocarriers formulation strategies explored. The aim of this work is to offer an overview of the antisense technology with a comparative analysis of the oligonucleotides approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA).

Keywords: antisense oligonucleotide; gene silencing; genetic disorder; pharmacology; siRNA.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

FIGURE 1
FIGURE 1
Mechanism of action of antisense oligonucleotides. Antisense oligonucleotides and siRNA can be used to target a specific, complementary (coding or non-coding) RNA. Main mechanisms of actions are: 1) RNA cleavage through the recruitment of endogenous enzymes; 2) Steric hindrance; 3) Splicing modulation; 4) Activation of RISC complex by the double-stranded siRNA. ASO, antisense oligonucleotides; aODN, siRNA: small-interfering RNA; RNase H, Ribonuclease H; RISC, RNA inducing silencing complex; mRNA, messenger RNA.
FIGURE 2
FIGURE 2
Oligonucleotide drugs approved by FDA and EMA. ASO drugs for different therapeutic areas (neurological and neuromuscular, metabolic and endocrine, and infection diseases) approved by the Food and Drug Administration and European Medicines Agency from 2013 to 2022.
See this image and copyright information in PMC

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