The powerful world of antisense oligonucleotides: From bench to bedside.

Anaïs M Quemener,David Gilot,Laura Bachelot,Marie‐Dominique Galibert,Emmanuelle Donnou‐Fournet,Anne Forestier

doi:10.1002/wrna.1594

Abstract

Antisense oligonucleotides (ASOs) represent a new and highly promising class of drugs for personalized medicine. In the last decade, major chemical developments and improvements of the backbone structure of ASOs have transformed them into true approved and commercialized drugs. ASOs target both DNA and RNA, including pre‐mRNA, mRNA, and ncRDA, based on sequence complementary. They are designed to be specific for each identified molecular and genetic alteration to restore a normal, physiological situation. Thus, the characterization of the underpinning mechanisms and alterations that sustain pathology is critical for accurate ASO‐design. ASOs can be used to cure both rare and common diseases, such as orphan genetic alterations and cancer. Through pioneering examples, this review shows the versatility of the mechanisms of action that provide ASOs with the potential capacity to achieve custom treatment, revolutionizing personalized medicine.This article is categorized under:RNA in Disease and Development > RNA in DiseaseRNA Interactions with Proteins and Other Molecules > Small Molecule–RNA Interactions

Highlights

Recent improvements in pharmacology, together with an understanding of the molecular mechanisms underlying diseases, have led to significant advances in the therapeutic management of patients
High throughput sequencing has made it possible to perform powerful molecular diagnoses required for the characterization of gene alterations and the implementation of targeted therapies
Through a non-exhaustive set of pioneering examples, we show here that Antisense oligonucleotides (ASOs) can be used to treat many diseases caused by diverse genetic alterations and molecular programs

Summary

Introduction

Together with an understanding of the molecular mechanisms underlying diseases, have led to significant advances in the therapeutic management of patients. Personalized and precision medicine is becoming essential, alongside more general and sometimes only symptomatic treatment. Personalized medicine is adapted to the genetic, molecular, and phenotypic characteristics of the disease and the patient, by targeting causative components. One of the major challenges in the current management of many diseases is predicting the responses to treatment as a function of patient-intrinsic characteristics. There is, a genuine revolution underway in patient care.

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