Yeast cell factory for mRNA bioproduction

Voices of Leading Scientists on the Occasion of Two Years of Yscript – Dr Fani Sousa

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 Fani Sousa, Associate Professor at University of Beira Interior:

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?

“For the past two years, we have been working on the purification of mRNA. The isolation of this biomolecule is very challenging due to the complexity of the samples and the similarity of most of the impurities. The purification process and conditions are being studied and optimised, and we expect to be able to apply the established conditions for the purification of mRNA produced in yeast, and clarified by the innovative method under development, to take advantage of the integrated strategy. At this stage, we can consider as a significant advance the possibility of promoting the removal of major impurities from mRNA-containing samples with the technology under development.”

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?

“The purification of mRNA presents a number of challenges, and it is essential to have an effective process in place to ensure the high purity and quality of this product in order to guarantee the efficacy and safety of mRNA in therapeutic applications. On the one hand, it is essential to be able to recover the previously clarified product in order to avoid product loss and yield reduction. On the other hand, the selective purification of the mRNA and the elimination of impurities must be carefully optimised to improve the purity, yield, and stability of the mRNA. The purification method under evaluation aims to use mild and specific conditions to overcome the main challenges and ensure mRNA quality.”

Looking ahead, what steps are you looking forward to?

“The team is pursuing the establishment of an effective mRNA purification process that will allow integration into the streamline designed for the production, isolation, and purification of this product. The development of this integrated platform is one of the most challenging aspects of the Yscript project, but we expect it to be the most significant technological breakthrough.”

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 greatly benefits from the expertise of the partners involved. Some of the collaborations were already underway before the project started, which facilitates communication, organisation of tasks and work, and full articulation for the accomplishment of the project. All partners are very focused on the success of Yscript.”

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?

“This experience with the European programme has been challenging from the application to the execution of the project, as it is a very competitive programme dedicated to funding and supporting highly disruptive ideas rather than incremental approaches. However, this pressure pushes researchers to develop innovative ideas and push boundaries in order to have a real impact on society.”

Dr Fani Sousa, Associate Professor at University of Beira Interior