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The recent article “Recent Update on siRNA Therapeutics” from the International Journal of Molecular Sciences provides a comprehensive analysis of the state of siRNA-based therapies. Its conclusions are key to understanding where the sector is heading and why infrastructures such as those developed in the project SYOLIGO are essential for the industry in Europe.
A precise mechanism with far-reaching clinical implications
An siRNA generally acts by interfering with gene expression and degrading the target mRNA before it is translated into protein. This precision has driven siRNA research in multiple therapeutic areas, from rare diseases to cancers, viral infections, and neurodegenerative diseases.
The field has advanced rapidly and there are already approved therapiessuch as Patisiran, Givosiran and Inclisiran, which have demonstrated that this modality is effective and scalable in real patients.
Current challenges: stability, cellular delivery and immune response.
Although siRNA has enormous therapeutic potential, the paper highlights several technical challenges that still need to be resolved. One of the main challenges is effective delivery to the target organ or tissue, as these molecules require advanced vehicles that prevent their degradation, improve cellular absorption, and ensure adequate biodistribution. Among the most promising strategies are LNPs, GalNAc conjugates, exosomes, and polypeptide nanoparticles. Added to this is the need to improve the stability of siRNA against nucleases, which is addressed through chemical modifications that increase its resistance and prolong its half-life. Another relevant challenge is to avoid immune activation, as lengths greater than 30 nucleotides can induce unwanted interferon responses. Finally, although the article points out that some siRNA-based therapies can reach high annual prices (between £300,000 and £1,200,000), these figures refer to the overall cost associated with drug development, including research, clinical trials, and regulatory processes. Production under GMP conditions remains demanding and requires rigorous controls, but these amounts do not represent the direct cost of manufacturing siRNA, but rather reflect the entire journey involved in bringing an RNA therapy from the laboratory to the patient.
Production: the major bottleneck to be resolved
The paper emphasises a critical point: the industry urgently needs more efficient, scalable and sustainable manufacturing processes.
Solid-phase synthesis, the most widely used method for manufacturing oligonucleotides, requires large quantities of solvents and reagents, which affects both the cost and the environmental impact.
In addition, manufacturing must comply with rigorous GMP requirements, with comprehensive purity, stability and endotoxin controls.
The article also shows that nanocarriers add additional complexity, as they require strict consistency in size, shape, and surface area to ensure reproducible behaviour in patients.
Future prospects: towards more precise and accessible therapies
Despite the challenges, the paper’s conclusions are optimistic:
- Research continues to improve the selection of therapeutic targets through omic and computational technologies.
- Innovations in delivery vehicles are expanding clinical possibilities.
- The combination of siRNA with gene editing or traditional therapies may open up new treatment strategies.
- Demand for therapeutic siRNA will continue to grow, especially in rare diseases and liver, eye and infectious diseases.
Why all this matters for Europe and for the SYOLIGO project
The challenges described in the paper confirm a strategic reality:
Europe needs its own capacity for the sustainable, scalable and affordable manufacture of therapeutic oligonucleotides.
The analysis highlights the sector’s dependence on:
- optimised and less polluting synthesis processes,
- advanced GMP infrastructures,
- innovation in synthetic routes and purification technologies,
- close collaboration between academia, industry and regulators.
This reinforces the relevance of projects such as SYOLIGO, which seek precisely:
- modernise and make oligonucleotide production sustainable,
- equip Europe with technological autonomy,
- accelerate access to RNA therapies for the patients who need them most.
In short, the development of siRNA-based therapies is transforming the biomedical landscape. Its precision and potential make this technology key to tackling previously untreatable diseases. But its advancement depends on solving technical and production challenges that require industrial innovation, scientific excellence, and sustainable manufacturing capabilities.
Europe has the opportunity to lead this biotechnology revolution, and strengthening its production infrastructure will be essential to ensuring that the next generation of RNA therapies reach those who need them most.
