MicroRNAs in In Vitro Diagnostics: Promises and Challenges

MicroRNAs and in vitro diagnostics: from the laboratory to the clinic

miRNAs are short non-coding RNAs, generally 19 to 25 nucleotides long, that regulate gene expression by inhibiting translation or degrading messenger RNA. A major asset of miRNAs is their stability: encapsulated in exosomes or bound to proteins, they resist unfavorable conditions, allowing their detection in various biological fluids (blood, urine, saliva).

In the field of in vitro diagnostics, several miRNA detection techniques are employed. RT-qPCR remains the “gold standard” for targeted quantification due to its sensitivity and specificity, while microarrays and next-generation sequencing (NGS) provide global expression profiles. Each of these methods presents advantages and limitations in terms of cost, processing time, and reproducibility, justifying growing interest in standardizing protocols.

The expression profiles of microRNAs have already been exploited for the early diagnosis of numerous pathologies such as certain cancers, cardiovascular diseases, or neurological disorders. For example, recent studies show that a set of miRNAs can help differentiate, with high sensitivity and specificity, patients with a particular pathology from those with healthy states or other conditions. Thus, microRNA signatures offer the advantage of a non-invasive, rapid diagnosis potentially integrated into automated devices.

Potential prospects of microRNA technology

In vitro diagnostic tests, particularly those based on molecular biomarkers, are booming. These molecular signatures, when combined with other classical biomarkers (such as proteins), can improve diagnostic accuracy and more effectively guide therapeutic strategies.

Advances in microRNA analysis offer several interesting prospects for in vitro diagnostics:

• Early and personalized diagnosis: The integration of miRNA profiles into decision support algorithms could enable early identification of diseases such as cancer, even before the appearance of clinical symptoms, thus paving the way for personalized therapeutic interventions.
• Monitoring treatment response: Dynamic monitoring of miRNA expression could be used to track treatment effectiveness, allowing therapeutic protocols to be adjusted in real time and optimizing patient care.
• Development of innovative diagnostic devices: The combination of microfluidic technologies, nanotechnology, and artificial intelligence promises the development of integrated multiplex platforms capable of detecting several microRNAs from very small sample volumes, thus reducing costs and diagnostic time while meeting current clinical needs.

These prospects, while promising, face barriers that must be overcome to confirm their applicability and robustness.

Challenges and barriers to overcome

Despite these opportunities, several challenges remain. The integration of microRNAs into clinical diagnostics encounters several obstacles:

• Standardization of protocols: The diversity of extraction and quantification methods leads to variability in results. It is crucial to develop international standards to ensure data reproducibility between laboratories.
• Large-scale clinical validation: Most current studies are based on small cohorts. Rigorous clinical trials on large populations are necessary to establish the diagnostic robustness of miRNAs.
• Complexity of biological interpretation: MicroRNA levels can be influenced by numerous physiological and pathological factors, generating inter-individual variability making their interpretation complex. A fine understanding of their regulation and their interactions with other biological pathways is still underway.
• Regulatory constraints and investments: Regulatory requirements (FDA, EMA) for validating diagnostic tests based on molecular biomarkers represent a significant challenge, requiring investments in R&D and infrastructure to meet quality and safety standards.

These challenges have been clearly highlighted in the literature by researchers, who call for increased collaboration between researchers, industry players, and regulatory authorities.

MicroRNAs offer considerable potential for in vitro diagnostics thanks to their stability, expression specificity, and ability to reflect a patient’s pathological state. Nevertheless, their clinical integration is still in its early stages and requires method standardization, robust clinical validation, and adaptation to regulatory requirements. The future prospects (including early diagnosis, personalized monitoring, and development of integrated devices) are promising, but must be approached with caution, particularly in terms of method standardization and clinical validation.

For stakeholders in the sector, whether biotechs, pharmaceutical groups, or technology providers, investing in microRNA research represents an opportunity for disruptive innovation in diagnostics. Alcimed can support you in your project, feel free to contact our team!

About the author,
Antoine, Consultant in Alcimed’s Healthcare team in France.