antisense oligonucleotide
Meaning of antisense oligonucleotide: A short synthetic strand designed to pair with one chosen message inside a cell and either destroy it or reroute it.
Definition of antisense oligonucleotide
An antisense oligonucleotide is a short, chemically modified strand of nucleic acid built to pair with a chosen stretch of RNA inside a cell. Binding either marks that RNA for destruction or physically blocks the machinery that reads it, so the protein it codes for is reduced or altered. Several are approved medicines for inherited disorders.
What does antisense mean?
DNA has two strands. One carries the message in readable form and is called the sense strand; the other is its mirror image and is called antisense. A drug built to the antisense sequence will therefore stick to the message, because the bases pair in only one way. That specificity is the whole appeal. A strand of fifteen to twenty five bases matches one place in the entire genome, so a single protein can be targeted directly, where a conventional drug has to find a pocket on the surface of the finished protein instead.
What happens after it binds?
| Mechanism | Result |
|---|---|
| Recruits a cutting enzyme | The target RNA is destroyed and less protein is made |
| Blocks without cutting | Reading is obstructed, or the message is assembled differently |
The second mechanism is the more surprising one, because it can add function rather than remove it. Directing the splicing machinery to skip a damaged section, or to include one it had been leaving out, can turn a protein that does not work into one that partly does. Approved drugs of this kind treat spinal muscular atrophy and a form of muscular dystrophy.
Why is it not just a piece of DNA?
Unmodified DNA in the bloodstream is destroyed within minutes and enters cells poorly. Every practical drug in this class is chemically altered, usually along its backbone and on its sugars, so that it resists those enzymes and lingers long enough to act. Delivery remains the limiting problem. The liver and kidney take these molecules up readily, which makes diseases of those organs the easiest targets, while reaching the brain means injecting into the fluid around the spinal cord. Early hopes that the class would prove broadly useful against cancer were not borne out, and it found its place in rare inherited disease instead. The older name antisense agent covers the same molecules.
Also known as
Used in a sentence
An antisense oligonucleotide was given by injection into the spinal fluid.
Good to know
These are chemically modified analogues rather than plain DNA or RNA, and their established successes lie in inherited neuromuscular and metabolic disease rather than in cancer, where trials have largely disappointed.
Word origin
Where “antisense oligonucleotide” comes from
Oligonucleotide joins the Greek oligos, meaning few, with nucleotide, the unit of nucleic acid; antisense names the strand mirroring the readable, or sense, sequence.