The powerful world of antisense oligonucleotides: From bench to bedside

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.

LncRNA SNHG3, a potential oncogene in human cancers

“…After these small RNAs (sRNAs) are incorporated into miRNA or siRNA-induced silencing complex (RISC), they participate in gene silencing in cells primarily through RNAi interference (RNAi) mechanisms [ 86 , 87 ]. What’s more, antisense oligonucleotides (ASOs) are short single-stranded nucleic acid sequences, which form a stable hybrid with its target mRNA, thereby interfering with its processing or translation [ 88 ]. Although small ncRNAs have proven to be promising in vitro effective therapeutic drugs, it is very difficult to deliver these nucleic acid drugs into cells, and the low bioavailability of these nucleic acid drugs in vivo remains a major challenge.…”

Emerging Role and Therapeutic Potential of lncRNAs in Colorectal Cancer

“…As for siRNAs, these changes can target phosphates, riboses, and bases. However, beside the phosphorothioate (PS), locked nucleic acid (LNA), and 5′methylcytosine (5mc) modifications, most chemical changes inhibit the recruitment of and activity of RNAse H [ 167 , 168 ]. While modifications like 2′-O methyl (2′O-Me), and phosphorodiamidate morpholino oligomers (PMOs) would most likely block the activity of RNAse H by steric hindrance, they could be exploited to promote conformational/structural changes or to interfere with specific interactions mediated by an RNA of interest.…”

Overview of Epstein–Barr-Virus-Associated Gastric Cancer Correlated with Prognostic Classification and Development of Therapeutic Options

“…Today, the approach is still in its infancy, with no ongoing trials for EBVaGC therapy. A similar approach involves using antisense oligonucleotides which are complementary to messenger RNA (mRNA), instead of miRNA for intracellular genes overexpressed in cancers, to mediate change in the behavior of malignancies [166]. To date, FDA has approved antisense drugs for some non-tumor genetic disorders (e.g., [167][168][169]).…”