title: Phosphorothioate oligonucleotides: effectiveness and toxicity.
abstract: 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.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Iannitti
authors.forename: Julio Cesar
authors.initials: JC
authors.lastname: Morales-Medina
authors.affiliation: School of Biomedical Sciences, University of Leeds, Mount Preston Street, Garstang building, LS2 9JT, UK. tommaso.iannitti@gmail.com.
authors.forename: Beniamino
authors.initials: B
authors.lastname: Palmieri
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D004353:Drug Evaluation, Preclinical; D006801:Humans; D054735:Phosphorothioate Oligonucleotides / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use* / Q000633:toxicity*; D016896:Treatment Outcome
chemical_list: D054735:Phosphorothioate Oligonucleotides