Katerina Leonida from Larissa, Greece, is a doctoral candidate who recently took on the DC8 project within the MCSA Doctoral Network GET-IN (www.get-in.org). Part of Horizon Europe, MSCA - Marie Skłodowska-Curie Actions - is the European Union’s flagship funding programme for doctoral education and postdoctoral training of researchers. Katerina Leonida: "The aim of my PhD is to develop a detailed digital twin of upstream unit operations for AAV-based gene therapy manufacturing. This will enable model-based optimization of the manufacturing process. To meet the increasing demand for gene therapies, it is essential to develop new production methods and address various critical obstacles related to processes and technologies. My PhD project with GET-IN is conducted in close collaboration with partner Antleron in Leuven, Belgium."
Digital twin for AAV-based gene therapy manufacturing
Gene therapy product development is significantly more complex than traditional drug and antibody discovery. Standardizing and controlling the process is more challenging due to the need for in-depth optimization of manufacturing methods, cost management, and quality control procedures tailored to each specific product.
The MCSA Doctoral Network GET-IN aims to address significant knowledge gaps that currently hinder the widespread adoption of gene therapies, including biomanufacturing productivity, gene editing efficacy, and organ-on-chip technology. For the DC8 doctoral project, Katerina Leonida from Greece was selected by GET-IN and partner Antleron: "My goal is to develop a detailed digital twin for AAV-based gene therapy manufacturing. This will enable model-based optimization of novel manufacturing processes, making them more practical, straightforward, and cost-effective to scale reliably and economically."
A chemical engineer with a natural interest in biology
Katerina Leonida earned her master's degree in chemical engineering from Aristotle University of Thessaloniki, dedicating her master’s thesis to researching algal cultures. Her interest in biology began during her student years. As an undergraduate, she participated in iGEM, the international synthetic biology competition, where her team proposed an innovative treatment for Glioblastoma brain cancer using a molecular theranostic tool based on the Hybridization Chain Reaction (HCR) technique. This theranostic approach combines therapy and diagnosis to precisely target Glioblastoma, offering a higher safety profile and fewer side effects. The Aristotle University team won the Entrepreneurship nomination for their project at the finals in Paris.
The digital twin being developed within GET-IN will utilize a proprietary combination of hybrid models and computational fluid dynamics (CFD) to fast-track process optimization towards predefined objectives and develop custom processes for gene therapies. Katerina explains, "We will implement ways to further extend the current limited knowledge about data-driven and hybrid models in the context of the kinetic and mechanistic models used in the digital twin. Rather than merely reporting titer or productivity metrics, the model output will offer quantitative descriptors for key Critical Quality Attributes (CQAs). These descriptors will be developed in collaboration with my fellow GET-IN PhD students, who are contributing across the gene therapy value chain. This will provide significant advantages for non-destructive process monitoring and control."
Part of a broader network focused on gene therapy innovations
The digital twin will be calibrated and validated against experimental data from literature, in-house data from Antleron, and data generated within GET-IN. Katerina explains, "During this process, I will collect experimental data sets and use parametric uncertainty analyses to examine how the variability of critical process parameters influences product CQAs. Following this, I will determine the optimal ‘process operating window’ using multi-parametric optimization. Multi-parameter simulations will allow me to further reduce the number of necessary laboratory experiments. This is how the digital twin significantly decreases the time and cost required to optimize such complex processes."
In the coming years, Katerina will primarily focus on developing the digital twin to support model-based optimization of AAV-based gene therapy manufacturing. Katerina states, "I am excited to collaborate with the international team of PhD students working on the GET-IN project. At Antleron, I am fortunate to be surrounded by an enthusiastic team of seasoned specialists across a wide range of disciplines. They are instrumental in developing innovative, (personalized) therapy focused bioprocesses that can be scaled flexibly and economically."
This PhD project may serve as a steppingstone toward my future goal of starting a career in applied research supporting medicine manufacturing. In the meantime, I have moved to Belgium, where I have met with professors, researchers, and fellow students at KU Leuven, as well as the team of specialists at Antleron. Later, my PhD will also take me to London and back to Thessaloniki.
A researcher who is also a globetrotter and coffee lover
"In my free time, I love exploring the world and experiencing different climates and cultures while tasting local dishes. I am a coffee enthusiast, and I occasionally enjoy cooking. Spending time with family and friends is one of my favorite pastimes. Additionally, I enjoy watching movies, going to the gym, and expanding my postcard collection."
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