Yeast cell factory for mRNA bioproduction

Informations projet

Yscript

N° de convention de subvention: 101047214

DOI

10.3030/101047214

Projet clôturé

Date de signature de la CE 15 Mars 2022

Date de début 1 Avril 2022

Date de fin 30 Septembre 2025

Financé au titre de

• The European Innovation Council (EIC)

Coût total

€ 3 079 675,00

Contribution de l’UE

€ 3 078 249,75

Coordonné par

UNIVERSITE D'ORLEANS
France

Periodic Reporting for period 2 - Yscript (Yeast cell factory for mRNA bioproduction)

Période du rapport: 2023-04-01 au 2025-09-30

Résumé du contexte et des objectifs généraux du projet

Messenger RNA (mRNA) vaccines have become a game-changer in the fight against COVID-19. mRNA is now considered a future of biomedicine for a vast array of medical applications. Therapeutic mRNA is predominantly manufactured by in-vitro transcription (IVT), a route that relies on expensive enzymes, capped/modified nucleotides and intensive purification. Yscript’s vision is an economically sustainable, yeast-based factory that biosynthesizes mature, capped, poly(A)+ mRNA, nucleoside-modified mRNA thereby reducing dependency on synthetic reagents and enabling rapid, flexible production of diverse mRNA therapeutics.
by . The project’s objectives are to engineer strains that accumulate intact, translatable mRNA targeted in membrane-less intracellular comparments; to establish a robust bioprocess that is reproducible and scalable; to integrate a cost-effective extraction and purification train; and to deliver high-quality mRNA, including cap1, with an extension pathway toward novel RNA formats. The expected pathway to impact is a streamlined, EU-based manufacturing route that reduces reliance on synthetic reagents, improves responsiveness to new targets, and supports equitable access to mRNA therapeutics through lower production costs and faster re-targeting.
Our consortium brings together the unique skill sets and expertise of seven partners across Europe from basic RNA biology to industrial expertise. UO and CNRS (France) combines world-class expertise in mRNA therapeutics and yeast mRNA processes. TRON (Germany) develops advanced novel platforms for individualized therapies and vaccines, exploit its extensive experience in engineering self-amplifying mRNA and immunological in vivo models. IBCH (Poland) uses its solid experience in mRNA biophysics to optimize mRNA accumulation in specific compartments. INRAE (France) leverages its experience as a pre-industrial demonstrator to upscale the process to a pre-industrial scale. UAVR (Portugal) brings its unparalleled knowledge on the development of cost-effective integrated extraction-purification platforms based on ionic liquids, here applied to mRNA purification. UBI (Portugal) oversees the chromatographic conditions for mRNA purification, building on their world-class experience in nucleic acids purification and stabilization. BIASep/Sartorius, a leading developer of chromatographic columns, developped ligand-coupling modified mRNA purification columns. Finally, UO, TRON and INRAE performed technology validation and quality control.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

The project established and validated a yeast-based manufacturing concept for therapeutic mRNA. Through rational genetic design and precise intracellular targeting, we concentrated the messenger RNA of interest in a form compatible with recovery and translation, while demonstrating functional gains in mRNA quality within the host system. We achived to produce proprietary designs and analytical specifics without disclosing proprietary constructs or analytical parameters, ensuring a non-confidential presentation suitable for broad audiences.
Building on this foundation, we developed a robust, repeatable bioprocess and transferred it across successively larger scales under pre-industrial conditions. Process controls were introduced to minimise variability and sustain consistent output, while preserving the flexibility needed to retarget the platform to new indications. Although specific media, operating windows, and quantitative performance metrics remain protected, the successful scale transfer confirms readiness for pilot environments.
For the downstream process, we assembled an integrated sequence that supports recovery, effective clarification, and selective capture of the mRNA product, with impurity reduction aligned to recognised quality attributes. This upstream–downstream stack demonstrates clear feasibility for industrialisation and provides a credible path toward future GMP translation. In parallel, we defined several Key Exploitable Results—encompassing tools, processes, and know-how—that are progressing through appropriate protection and uptake routes. Depending on the asset, these include patenting under assessment, trade-secret stewardship, and licensing options for end-users, enabling timely adoption without disclosure of sensitive details.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

Yscript delivers results beyond the state of the art by establishing a microbial, yeast-based route for therapeutic mRNA that shortens the production–purification chain, embeds industrialisation requirements from the start, and remains flexible and rapidly re-targetable. Leveraging a simple, widely adopted organism, the platform is primed for broad diffusion and local manufacturing, enabling agile scale-up of RNA vaccines and medicines while easing cold-chain and distribution bottlenecks. By avoiding high-priced reagents, enabling parallel production of multiple mRNAs, and using a cost-effective cell factory, Yscript lowers costs and expands access—particularly for low- and middle-income populations and advancing SDG3. While , it also opens new therapeutic space for longer and more complex transcripts that are difficult to produce conventionally.
The process is designed under sustainability principles to reduce energy use, solvent consumption, and waste, supporting greener biomanufacturing. To accelerate uptake, the consortium is advancing protection and licensing of key exploitable results, initiating tech-transfer partnerships, and preparing assets for end-user adoption.
Next actions include pilot-to-GMP demonstrations with regulatory-grade analytics; targeted access to markets and finance through industrial partnerships; clear commercialisation and internationalisation pathways; and alignment with EU standards and regulatory guidance. The goal us to have the platform scale quickly, safely, and competitively across Member States.

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