Yeast cell factory for mRNA bioproduction

Voices of Leading Scientists on the Occasion of Two Years of Yscript – Dr Mara Freire

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 Mara Freire, Coordinator Researcher and Director of Group 5 (Biomedical and Biomimetic Materials) at CICECO – Aveiro Institute of Materials, University of Aveiro:

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?

“Over the past two years, our team has made significant efforts in advancing the purification of mRNA produced in yeast within the scope of Yscript. We already identified promising conditions for yeast lysis and mRNA clarification. Currently, our work is focused on optimising the set of conditions for both stages, ultimately allowing their integration. This will contribute to the development of a novel purification method that effectively separates mRNA from other cellular components in yeast lysates, which promises to significantly contribute to the advancement of mRNA-based therapies.”

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?

“During the past two years of our involvement in Yscript and given its high-risk/high-gain nature, we obviously faced several challenges inherent to research endeavours. One significant challenge was the development of an alternative and more biocompatible process for yeast lysis without compromising the purity, yield and integrity of the mRNA.”

Looking ahead, what steps are you looking forward to?

“I am eager to continue refining the aimed integrated mRNA purification process to enhance its efficiency, yield and purity. This will involve conducting additional experiments, fine-tuning parameters and exploring innovative purification techniques. As we progress towards the latter stages of the project, we need to consider the process scaling up. Even with high risks ahead, I am enthusiastic about the upcoming steps in the Yscript project and the opportunities they present for further innovation, collaboration and societal impact.”

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?

“The Yscript project has indeed been a challenging endeavour that has emphasised the importance of teamwork and collaboration. Over the past two years, I've had the privilege of working closely with amazing colleagues, who carry out research of excellence in their fields. Through collaborative efforts within our team and with other project partners, we are now on the way of optimising a promising process for yeast lysis and clarification. These experiences have not only strengthened our research capabilities but also improved our collaborative spirit.”

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?

“Being part of the Yscript project has provided a unique and enriching experience thus far. The EIC Pathfinder program offers a distinctive framework that fosters innovation and encourages high-risk, high-reward research endeavours. My experiences with the program have been highly positive. One notable aspect of the EIC Pathfinder program is its emphasis on disruptive technologies and breakthrough innovations. Unlike traditional EU-funded projects, which may focus on incremental advancements or specific research goals, the EIC Pathfinder encourages ambitious and visionary projects that have the potential to revolutionise entire fields, being the case of Yscript.”

Dr Mara Freire, Coordinator Researcher and Director of Group 5 (Biomedical and Biomimetic Materials) at CICECO – Aveiro Institute of Materials, University of Aveiro