Introduction: what are therapeutic oligonucleotides?
The fight against cancer is entering a new era, fuelled by a wave of innovation in precision and personalized medicine. Therapeutic oligonucleotides are to highlight in this regard: short, synthetic strands of nucleic acids that can modulate gene expression with unparalleled specificity. As science deepens our understanding of cancer at the molecular level, oligonucleotides are emerging as a powerful tool to target previously “undruggable” pathways. Several type of therapeutic oligonucleotides can be defined in this sense:
- Antisense oligonucleotides (AONs): Bind to mRNA to prevent translation or promote degradation.
- Small interfering RNAs (siRNAs): Harness the RNA interference pathway to silence specific genes.
- Aptamers: Structured oligonucleotides that bind proteins with high affinity, acting similarly to antibodies.
- miRNA mimics/inhibitors: Modulate endogenous microRNA pathways involved in cancer progression.
These molecules are designed to interfere directly with gene expression, allowing unprecedented precision in addressing genetic drivers of cancer. Their relevance in oncology is precisely driven by the fact that cancer often find its inception in genetic mutations, overexpression, or silencing of specific genes[1]. By employing therapeutic oligonucleotides, we are able to:
- Targeting non-coding RNAs and intracellular targets not accessible to small molecules or antibodies.
- The ability to modulate gene expression at the RNA level, before disease-driving proteins are even produced.
- Potential for tissue-specific delivery, especially using lipid nanoparticles or ligand-based targeting.
Therapeutic oligonucleotides can be engineered to be tumour-specific, reduce systemic toxicity, and minimize off-target effects — a vital need in oncology.
How are they fitting in the market?
Therapeutical oligonucleotides are not only attractive for oncology purposes from a theoretical perspective, but are also gradually finding their place in the market through both KOLs acceptance and regulatory clearance:
- Accelerated approvals: FDA and EMA have already approved oligonucleotide-based drugs for rare genetic diseases, and oncology is now in focus.
- Big Pharma interest: Companies like AstraZeneca, Ionis Pharmaceuticals, and Alnylam are investing heavily in oligo-RNA platforms[2].
- Clinical pipeline growth: Dozens of oligonucleotide therapeutics are in oncology clinical trials, targeting solid tumours and haematological malignancies[3].
- AI & bioinformatics are increasingly used to design safer and more efficient oligos, with better off-target prediction and immunogenicity control[4].
- Delivery breakthroughs: Nanoparticles, exosomes, and antibody-oligo conjugates are enabling targeted delivery to tumour tissues[5].
Furthermore, this targeted market is extremely appealing in terms of size with $15 billion figure being achieved by 2030, with oncology as a key driver. Aligned with this, investment in RNA-based therapies hit record highs in the past three years, signalling strong confidence in the modality’s future.
Conclusion
As our understanding of cancer deepens at the molecular and transcriptomic levels, therapeutic oligonucleotides are emerging as a powerful tool to transform this knowledge into highly targeted treatments. These molecules hold significant promise for tackling cancers that have proven resistant to traditional therapies — and may well shape the future of oncology. @TAONAS LUAD is at the forefront of this trend, advancing innovation in the field.
Author: Marc Domínguez
Date: June, 2025
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[1] Bonnal SC, et al. Nat Rev Clin Oncol 17:457-474 (2020)
[2] https://oligofastx.com/innovation-on-the-horizon-how-big-pharma-investment-is-driving-the-development-of-oligonucleotide-based-medicines/
[3] Xiong, H., Veedu, R. N., & Diermeier, S. D. (2021). Recent advances in oligonucleotide therapeutics in oncology. International Journal of Molecular Sciences, 22(7), 3295.
[3] Amol D. Gholap, Abdelwahab Omri, Advances in artificial intelligence-envisioned technologies for protein and nucleic acid research, Drug Discovery Today, Volume 30, Issue 5, 2025,104362, ISSN 1359-6446, https://doi.org/10.1016/j.drudis.2025.104362.
[5] Roberts, T. C., Langer, R., & Wood, M. J. (2020). Advances in oligonucleotide drug delivery. Nature reviews Drug discovery, 19(10), 673-694.