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Serious science. Curious minds.
Engineering next-generation RNA therapeutics inspired by extracellular vesicles
Congratulations, Dr Guénolé Tossou!
Guénolé successfully defended his PhD on October 13, 2026, at Université Paris Cité.
A PhD is measured in experiments, figures and papers, but also in everything that happens in between: unanswered questions, experiments that need to be started again, discussions that change the direction of a project, and the perseverance required to keep moving forward.
Over these years, I have had the chance to see Guénolé take full ownership of his project, develop his scientific independence, and carry the work all the way to a first-author publication in Molecular Therapy.
Beyond the science, what I will remember most is the journey we shared: the discussions, the doubts, the excitement when an experiment finally worked, and all those moments that make a PhD much more than a collection of results.
Congratulations, Guénolé Tossou, on this remarkable achievement.
I feel fortunate to have shared this chapter with you and look forward to seeing where the next one takes you.
NEW PUBLICATION · 2026
NEW PUBLICATION · 2026
A combinatorial EV-miRNA signature mediates the anti-tumoral activity of NFAT3-regulated extracellular vesicles in aggressive cancers
A combinatorial EV-miRNA signature mediates the anti-tumoral activity of NFAT3-regulated extracellular vesicles in aggressive cancers
Molecular Therapy · Tossou et al., 2026
Molecular Therapy · Tossou et al., 2026
After several years of collaborative research, we are pleased to share that our team's latest study has been published in Molecular Therapy.
This publication marks an important milestone in our long-term research program dedicated to developing combinatorial RNA-based therapeutic strategies inspired by extracellular vesicles (EVs).
Triple-negative breast cancer (TNBC) and pancreatic cancer remain among the most aggressive human malignancies, highlighting the need for innovative therapeutic approaches.
Our research has been driven by a simple but fundamental question:
Can the anti-tumoral activity of extracellular vesicles be recapitulated by a defined combination of regulatory microRNAs?
In this study, we demonstrate that a defined signature of 15 microRNAs recapitulates the anti-tumoral activity of NFAT3-regulated extracellular vesicles. By coordinately regulating multiple pathways involved in tumor progression, this miRNA signature reduces cancer cell proliferation and invasion while displaying significant anti-tumoral activity in preclinical models.
These findings strengthen the concept that combinatorial RNA therapeutics may offer a promising strategy to tackle the molecular complexity of aggressive cancers.
More broadly, this work represents an important step toward translating the biological activity of extracellular vesicles into defined, programmable RNA therapeutics.
This publication is both a major milestone and the beginning of a new chapter in our research toward next-generation RNA therapeutics inspired by extracellular vesicles.
Behind the paper
What if we had asked the wrong question?
Our 2026 Molecular Therapy paper did not begin with miR-Comb 15. It began several years earlier with an unexpected biological observation — and a question.
2020 — THE DISCOVERY
2020 — THE DISCOVERY
In 2020, we discovered that NFAT3-regulated extracellular vesicles (EVs) possess anti-tumoral properties, reducing cancer cell invasion and limiting tumor progression and metastasis.
Scientific reports: Camargo et al.,2026
This discovery raised a fundamental question:
What makes these EVs anti-tumoral?
A natural next step would have been to study how cancer cells respond to EV treatment: which genes are modified? Which pathways are affected?
But our goal was not only to describe the cellular response. We wanted to identify the molecular information responsible for the anti-tumoral activity of these EVs.
If we could decipher the key actors carried by these vesicles, we might ultimately be able to harness this natural mechanism and transform it into a new therapeutic strategy against cancer.
So we asked a different question:
What molecular information do these EVs actually deliver to recipient cancer cells?
FROM THE RESPONSE TO THE MESSAGE
FROM THE RESPONSE TO THE MESSAGE
Rather than focusing only on cellular responses, we investigated the RNA cargo of NFAT3-regulated EVs.
Our hypothesis was that their activity was not driven by a single molecule, but by the coordinated action of multiple regulatory RNAs.
2026 — DECODING THE MESSAGE
2026 — DECODING THE MESSAGE
This strategy provided an answer: miR-Comb 15, a combinatorial 15-miRNA signature capable of recapitulating a large part of the anti-tumoral activity of NFAT3-regulated EVs.
Our Molecular Therapy study supports a broader concept:
Complex cancers may require combinatorial RNA therapeutics capable of modulating multiple molecular networks simultaneously.
From discovering an anti-tumoral EV function to decoding its functional RNA signature, this 2020 → 2026 journey illustrates how understanding a natural biological mechanism can inspire the development of next-generation programmable RNA therapeutics.
The mechanism at a glance
How do NFAT3-regulated extracellular vesicles suppress tumor progression?
How do NFAT3-regulated extracellular vesicles suppress tumor progression?
Our study reveals how a combinatorial miRNA cargo can translate the biological activity of NFAT3-regulated extracellular vesicles into coordinated regulation of multiple tumor-associated pathways.
Take-home message
A defined 15-miRNA signature recapitulates a large part of the anti-tumoral activity of NFAT3-regulated extracellular vesicles, supporting a multi-target RNA-based strategy to address the molecular complexity of aggressive cancers.
Our work highlighted in Molecular Therapy
Our work highlighted in Molecular Therapy
Our study has been highlighted in a dedicated Molecular Therapy Commentary:
Fifteen miRNAs, one network: Rethinking single-target therapy for aggressive cancer
In this Commentary, Jürgen Wittmann discusses our findings in the broader context of cancer therapy and highlights the potential of combinatorial miRNA strategies to move beyond the conventional single-target paradigm.
Highlighted by Université Paris Cité
Université Paris Cité has published a feature presenting our recent Molecular Therapy study to a broader audience, highlighting the identification of miR-Comb 15 and its potential as a framework for combinatorial RNA therapeutics in aggressive cancers.
Highlighted by Inserm
Unserm has featured our recent work on miR-Comb 15 and combinatorial RNA therapeutics in aggressive cancers through its national “Image de science” communication.
The post highlights our strategy of using a defined 15-miRNA combination to simultaneously target several cancer-driving programs, with activity demonstrated in breast and pancreatic cancer models and significant tumor-growth inhibition in vivo.
Highlighted by the Institut de Recherche Saint-Louis
The Institut de Recherche Saint-Louis featured our study, published in Molecular Therapy that identifies a combination of 15 miRNAs (miR-Comb-15) and reproduces the antitumor activity of NFAT3-regulated extracellular vesicles and acts on multiple aspects of tumor aggressiveness.
Many thanks to the IRSL for highlighting this work and to all the colleagues who contributed to it.
Featured in Drug Discovery News
Our Molecular Therapy study was featured in Drug Discovery News, highlighting miR-Comb-15 as a combinatorial RNA strategy for targeting multiple cancer-driving networks in aggressive cancers.
The article discusses our work on NFAT3-regulated extracellular vesicles, the identification of the 15-miRNA combination, and its potential as a framework for developing multi-target RNA therapeutics.
READ THE DRUG DISCOVERY NEWS FEATEURE→
→ Combinatorial miRNA signature curbs tumor growth in aggressive cancers”
Andrea Corona, Drug Discovery News, September 2026.
Our research in video — featured by Molecular Therapy
Molecular Therapy has shared our video summary presented by Guénolé Tossou and Sébastien Jauliac. Discover how miR-Comb-15, a combination of 15 microRNAs, reproduces the antitumor effects of NFAT3-regulated extracellular vesicles in preclinical models of aggressive cancers.
The story continues...
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