Antisense Oligonucleotide (AS‐ODN) Technology: Principle, Mechanism and Challenges

Abstract Recently, there is a hopefully tremendous interest in antisense therapeutics for clinical purposes. Single‐stranded synthetic antisense oligonucleotides (As‐ODNs) with monomers of chemically modified 18–21 deoxynucleotides complement the mRNA sequence in target gene. The target gene expression can be blocked because of created cleavage or disability of the mRNA by binding the As‐ODNs to cognate mRNA sequences via sequence‐specific hybridization. The idea of antisense therapy has become particular concerning that any sequence longer than a minimal number of nucleotides (17 for DNA and 13 for RNA) can be observed only once within the human genome. The mRNA is omnipresent more probably to manipulate compared to DNA, which results in multiple in vitro and in vivo applications for As‐ODNs in the field of regulatory mechanisms of biological processes, cancer, viral infections and hereditary impairments. Although, there are uncertain clinical outcomes on the ability of this approach in treatment procedures despite achieving promising findings based on previous investigations. Accordingly, the efficacy, off‐target effects, delivery are issues that should be investigated to obtain satisfactory results. In this review, we will explain the mechanism of action of As‐ODNs and various types of modifications and their therapeutic purposes.