Yeast cell factory for mRNA bioproduction

Voices of Leading Scientists on the Occasion of Two Years of Yscript – Dr Fayza Daboussi

In April 2022, Yscript embarked on a mission to develop a customised yeast-based messenger RNA factory platform for the large-scale and cost-effective production of mRNA therapeutics. After two years, we now look back together with our leading consortium members on the work done and progress achieved so far.

Read the interview with Dr Fayza Daboussi, Research Director at INRAE:

The past two years went by quickly, we are in the second half of the project now and a lot of work has already been conducted. What is the status of the work you are conducting in the project? What would you say is the biggest success/breakthrough that has been achieved so far?

“The work carried out by INRAE as part of the Yscript project has been very fruitful. Over the past two years, we have validated the proof of concept produced by our partner CNRS, demonstrating that a yeast cell factory can produce therapeutic mRNA. We have developed yeast strains with enhanced robustness for bioprocess development, engineering them to produce therapeutic mRNAs. Additionally, we created a culture medium compatible with industrial production processes and optimised the cultivation method in a 2L bioreactor to ensure scalable and efficient mRNA production.”

Research projects come with many uncertainties and challenges. What challenges came up in the course of the past two years and how did you manage to overcome them?

“INRAE's work on this project is highly challenging, focusing on developing a robust and efficient mRNA production process that increases yield and reduces manufacturing costs. The primary challenges include engineering a strain capable of sustaining scale-up and developing an optimal culture medium. By implementing mitigation plans at each stage and maintaining strong interactions with consortium partners, we have been able to reduce risks and accelerate development.”

Looking ahead, what steps are you looking forward to?

“Regarding our work, I am eager to conduct the proof of concept for producing various therapeutic targets to highlight the full potential of this disruptive technology. As for the project as a whole, I look forward to seeing my partners' results in cell lysis, mRNA purification, and functional testing. The integration of all these skills and expertise will demonstrate the technology's ability to reduce mRNA production costs and make it accessible to everyone.”

A challenging project like Yscript is teamwork. Have there been any personal encounters within or outside the consortium in the last two years that have had a lasting impact on you?

“Collaborating with internationally renowned scientists is an honour. I have never worked with the ones involved in this project before, and their commitment and innovative thinking are truly inspiring. The coordinator made an excellent choice by selecting individuals whose expertise complements each other perfectly.

After focusing on the chassis and the process, I will spend the next few months working on batch production. These batches will be used to optimise cell lysis, which is the crucial first step before the purification stages. I am looking forward to continuing our discussions with the teams and meeting them again at our annual meeting in Slovenia.”

Yscript is an EIC pathfinder project – how are your experiences with the programme so far? Do you see any difference to other EU funded projects you are involved in?

“It has been a great experience. This funding opportunity allows us to finance a risky, ambitious, and high-impact project. I am involved in a European distributed research infrastructure dedicated to industrial biotechnology, as well as disruptive INFRA-TECH projects. These calls for projects complement each other excellently.”

Dr Fayza Daboussi, Research Director at INRAE