Background: Many experimental and clinical studies have focused on the antisense strategy. In this context
phosphorothioate oligonucleotides are compounds addressed to hybridize to a targeted mRNA inducing a variety of effects
including inhibition of the expression of proteins involved in different pathological processes and preventing
translation. Methods: In this review, we provide an update on clinical efficacy and toxicological profile of phosphorothioate
oligonucleotides used in experimental and clinical studies, also focusing on the use of the antisense strategy
in the context of Duchenne muscular dystrophy which is a key pathology to study different aspects of this therapy.
Pubmed/Medline was searched using the keyword “Phosphorotioate” combined with “Antisense”, “Oligonucleotide”
and “Duchenne muscular dystrophy”. Conclusions: Phosphorothioate oligonucleotide transient activation of the complement
cascade represents the most evident toxicological response, as showed by in vivo studies. It is also known that
many of these compounds induce a prolongation of activated partial thromboplastin time, a reaction which is often
highly transient and proportional to the oligonucleotide plasma concentrations, making that effect clinically insignificant
for the current treatment regimens. In summary, current evidence shows limited untoward effects and reversibility
of the damage induced, at least for some of those compounds, with promising effectiveness for treatment of various pathologies.