The overarching goal of the ATTRACT group “FAST-PEP” was to take a holistic approach to bioprocess development in plant cells along the entire development chain and to address the central challenges in lead structure optimization, selection of expression systems, and development of a purification strategy (downstream processing, DSP).
The proposed solution aimed to combine predictive modeling with high parallelization, rational experimental design, and integrated data analysis. From the outset, lead structures were to be optimized using a systems biotechnology approach for both product yield and the key DSP-relevant properties (e.g., aggregation behavior).
An innovative approach combining integrated high-throughput protein expression and product purification was designed to overcome the current cost-intensive development bottleneck in DSP, enabling more efficient selection of product candidates. Drug candidates were to be preselected in silico based on their predicted expression, manufacturability (e.g., pH stability), and purifiability (e.g., charge properties), followed by rational structural optimization.
At the same time, mechanistic models were to be used to calculate optimal conditions for efficient purification of the candidates from contaminants present in each expression system. These predictions would then be empirically validated using statistical experimental design.
Based on the achieved yields, purities, and projected costs, an expert system would calculate the optimal sequence of process steps, ensuring a competitive production process for companies in the chemical, biotechnology, and pharmaceutical sectors.
Fraunhofer Institute for Molecular Biology and Applied Ecology IME
