‘Gene silencing’ is a term used to describe the process of stopping a specific gene from making its associated protein. It is different from ‘gene editing’ in that the gene itself is untouched; only its expression as a protein is affected.
One form of gene-silencing technology, antisense oligonucleotides (ASOs), has proved to be particularly effective, not least because it is highly targeted and produces far fewer side effects than gene editing.
In recent years, the market for ASO-based therapies has grown dramatically, with this growth forecast to continue over the next ten years, according to a number of industry analysts.
This article explains the science behind ASOs and explores the reasons for the predicted growth in the market. It also considers the barriers to that growth and the challenges faced by drug developers, especially as ASOs are seen as a key therapy for many rare diseases.
Cell out
Messenger RNA (mRNA) is a copy of DNA that leaves the cell nucleus for the ribosomes, where mRNA genetic code is translated into amino acids. These then grow into long chains that fold to form proteins.
ASOs are short, single- or double-stranded sequences of nucleotides, designed to bind to mRNA – stopping it from completing its function.
It is the ‘sense’ part of mRNA that results in a protein. ASOs are called antisense because they bind to the sense part of mRNA in a complementary manner, preventing it from producing its associated protein.
If a gene is known to have a specific mutation that leads to the production of a toxic protein, then that specific mutated gene can be targeted by an ASO, leading to a reduction in the volume of toxic protein produced.
In trials at University College London Hospitals (UCLH), an ASO is being used to target the mutated gene that results in the tau protein, which is one of two proteins (the other is amyloid) known to be prevalent in patients with Alzheimer’s. The trials have recently been extended after initial success.
Trials are also now underway for gene silencing ASOs that could treat Parkinson’s and motor neurone disease.
ASOs have shown to have particular benefits in the treatment of neurodegenerative diseases, including Duchenne muscular dystrophy and there are currently four ASO therapies for this condition that are approved by the FDA, demonstrating both effectiveness and market attractiveness.
Perhaps most importantly, ASOs target the molecular causes of disease, rather than just treating the symptoms. This is what makes them potentially game-changing.
Read the article in full here.