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Development of an Intensified Plasmid Production Process based on Continuous Lysis and Membrane Chromatography

The growing demand for plasmid DNA (pDNA) in gene therapy and vaccine development requires efficient and scalable production methods. Traditional batch lysis methods face limitations with long mixing times, high shear forces, and inconsistent lysis control. Additionally, resin-based purification is time-consuming and requires extra steps like RNA precipitation and tangential flow filtration (TFF). This work presents a continuous cell lysis device with low-shear pumps and a loop reactor for precise lysis control and minimal shear damage. Combined with Natrix® Q membrane chromatography, it allows high flow rates and RNA reduction without chemicals, optimizing conductivity for faster, cost-effective pDNA production with high supercoiled pDNA purity.

Author Antony Sibilia, Patrick Werder, Maike Otto, Alisa Strobel, Elena Wüstenhagen, Oliver Rammo, Thomas K. Villiger, Patrick Romann, Philip Giller
Company Levitronix GmbH, University of Applied Sciences Northwestern Switzerland, Merck Life Science KGaA
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