antisense oligonucleotide
An antisense oligonucleotide, or ASO, is a short single strand of genetic letters designed to be the mirror image of a specific messenger RNA. Because the two strands are complementary, the ASO snaps onto its target RNA like a piece of tape laid over a sentence, covering it so the cell can no longer read it correctly.
Once bound, an ASO can act in two main ways. Some ASOs simply block the RNA, jamming the machinery that reads it or that splices it, which can either silence a gene or redirect splicing to produce a better protein. Others form a DNA-RNA hybrid that flags the RNA for an enzyme called RNase H, which then cuts the target RNA and destroys it.
ASOs are single-stranded, which distinguishes them from double-stranded siRNA, and they rely heavily on chemical modifications to resist degradation and improve binding. Their reach is limited by delivery: most go to the liver, kidney, or, when injected into spinal fluid, the nervous system, and getting them efficiently into other tissues remains a major challenge.
Inotersen is an antisense oligonucleotide that triggers RNase H to degrade the transthyretin RNA, lowering production of a protein that builds up in nerves.
A single-stranded RNA-targeting drug that silences a gene by triggering RNA cleavage.
'Antisense' refers to the strand being complementary, the opposite or 'anti' sense, of the coding 'sense' RNA.