Antisense Oligonucleotides

Abstract

Antisense oligonucleotides or “ASO” are short-chained DNA sequences which are used to “turn off” genes. They achieve this by mechanisms such as activating an enzyme RNase which cleaves mRNA, by creating steric hindrance to the binding of mRNA to ribosomes, or by disrupting ribosome machinery. They can also be in the form of a silencing RNA when modified appropriately. Apart from a classification based on mechanism of action, they can also be classified by chemical types. ASOs are transported inside cells by receptors, endocytosis, and pinocytosis. Vectors are used only in in vitro experiments and not in in vivo. Challenges to their use include rapid degeneration, non-specific effects, and non-oral administration. Successful examples include fomivirsen (used in CMV retinitis), which targets the mRNA of cytomegalovirus, and mipomersen (used in hypercholesterolemia), which targets ApoB gene.