PROJECT DESCRIPTON
The objectives are:
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Enhance viral vector production efficiency by mapping the production process for retrovirus-based virus-like particles (VLPs) and rAAV and implementation of optimization algorithms.
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Improve the manufacturing environment using custom designed fixed-bed bioreactors (FBR) and optimize production conditions.
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Develop a closed, scalable manufacturing process to ensure patient safety.
The project focusses on the bioprocessing of rAAV and retroviral VLPs loaded with CRISPR-tools, the two main viral vector approaches used in LifeLUNG. The project involves wet lab experimental work, ranging from viral vector production, cell transfection and transduction, molecular biology, as well as in silico bioprocess modelling and bio-informatics. More specifically, it will involve experiments to improve production efficiency and optimizing production conditions. The DC will be using DoE, QbD, Bayesian modelling, Cost of Goods (CoG) modelling and digital twin solutions for process optimization (flow conditions, transfection conditions and ratios, production kinetics, harvest timings, …) to obtain a process that has both a high yield and is cost efficient.
A successful project will result in: Insight in the landscape of ATMP production, CoG analysis and process optimization. Modelling of the process environment, and exploration/comparison of production options in silico. Optimized production protocol for rAAV production and for CRISPR-VLP production (at least for one pseudotype and genetic payload). Establishment of a custom FBR and/or production cell line combination for rAAV/VLP production.
Enrolment in Doctoral School: KUL Doctoral school of Biomedical Sciences, thematic program Molecular Stem Cell Medicine, Faculty of Medicine
Planned secondments:
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Aarhus Universitet, Denmark (Prof. Jacob Giehm Mikkelsen): HIV-based VLP engineering and comparison with MLV-based VLPs (months 19-20)
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AstraZeneca AB, Sweden (Dr. Roberto Nitsch): compound library screen for rAAV and VLP production and transduction enhancers in human cell models (months 29-33)
ESSENTIAL REQUIREMENTS
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You hold a Master’s degree (no PhD) in bioscience engineering, biomedical sciences, (medical) biotechnology, civil engineering, medicine, pharmacy or a related field.
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You are passionate about life sciences and engineering, and want to achieve a PhD degree on the topic described in the description above
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You are ambitious, well organized and have excellent communication skills.
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You are proficient in English both spoken and written
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You have a solutions-oriented mindset that thrives in a multidisciplinary team
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You can work independently and have a constructive, critical mindset.
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You are an enthusiastic and motivated person, eager to participate in network-wide training events, international travel and public awareness activities.
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Willingness to travel
DESIRABLE SKILLS AND EXPERTISE
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Solid knowledge of cell biology, molecular biology and hands-on experience with mammalian cell culture (or other aseptic handling) is key
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Understanding of mammalian cell culture, virology and the viral vector production process (hands-on expertise is a plus)
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Understanding of RNAseq, proteomics and bioinformatic analysis in general, is a plus
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Engineering mindset
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Knowledge on process monitoring techniques and tools
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Statistical data analysis, Design-of-Experiments (DoE)
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Programming experience (preferably python) is an asset
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Knowledge on Numerical analysis (Computational Fluid Dynamics, Discrete Element Method) and Computer Aided Design (CAD) is a plus
ADVISED READING
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Trojan Horse-Like Vehicles for CRISPR-Cas Delivery: Engineering Extracellular Vesicles and Virus-Like Particles for Precision Gene Editing in Cystic Fibrosis. Dipalo et al. 2025 - https://pubmed.ncbi.nlm.nih.gov/40295092/
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Bayesian cell therapy process optimization. E. Claes et al. 2024 - https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/full/10.1002/bit.28669