Antisense Oligonucleotides: Treatment Strategies and Cellular Internalization

Abstract

The clinical applicaton of antisense oligonucleotides (ASOs) is becoming more of a reality as several drugs have been approved for the treatment of human disorders and many others are in various phases in development and clinical trials. ASOs are short DNA/RNA oligos which are heavily modified to increase their stability in biological fluids and retain the properties of creating RNA-RNA and DNA-RNA duplexes that knock-down or correct genetic expression. This review outlines several strategies that ASOs utilize for the treatment of various congenital diseases and syndromes that develop with aging. In addition, we discuss some of the mechanisms for specific non-targeted ASO internalization within cells.

Apolipoprotein C-III and cardiovascular diseases: when genetics meet molecular pathologies

“…In general, the ASO application is a newest type of pharmacological approaches pertaining to nucleic acid-based gene silencing [ 92 ]. Briefly, a heavily modified single-stranded deoxyribonucleotide can serve as a selective sequence that pairs to specific regions of a given mRNA, and regulates its translation into a functional protein [ 92 ].…”

“…In general, the ASO application is a newest type of pharmacological approaches pertaining to nucleic acid-based gene silencing [ 92 ]. Briefly, a heavily modified single-stranded deoxyribonucleotide can serve as a selective sequence that pairs to specific regions of a given mRNA, and regulates its translation into a functional protein [ 92 ]. The ASO can bind complementarily to the targeted mRNA by Watson–Crick hybridization and, in consequence, block the expression of this genetic material via many distinct mechanisms [ 92 ].…”

Introduction: An Overview of AI in Oncology Drug Discovery and Development

“…Once administration of the antisense oligonucleonucleotides was discontinued, receptor function and algesic responses returned. Unlike transgenic model, the antisense oligonucleotide effect is reversible [14].…”

Cancer Treatment: An Epigenetic View

“… 27 Antisense oligonucleotides (AO) are capable to modulating gene expression by interacting with specific gene transcripts by using various mechanisms. 28 …”