A Bioreactor-Based Yellow Fever Virus-like Particle Production Process with Integrated Process Analytical Technology Based on Transient Transfection
Abstract
1. Introduction
2. Materials and Methods
2.1. Plasmid Production
2.1.1. pDNA Production under Standard Conditions
2.1.2. Optimization of pDNA Production Using a Plackett–Burman Design
2.1.3. pDNA Purification
2.2. eGFP or YF-VLP Production
2.2.1. Cell Line and Medium
2.2.2. Transient Transfection in Shaking Flasks
2.2.3. Transient Transfection in a Stirred-Tank Bioreactor
2.3. Analysis
2.3.1. pDNA Analysis
2.3.2. Analysis of E. coli Growth
2.3.3. Offline Determination of Cell Concentration
2.3.4. Metabolite Analysis
2.3.5. SDS-PAGE
2.3.6. Western Blot
2.3.7. Imaging Flow Cytometry Measurement (IFCM)
2.3.8. Transmission Electron Microscopy (TEM)
2.3.9. Statistical Analysis
3. Results
3.1. Optimization of Transfection-Grade pDNA Production
3.2. Optimization of Process Parameters for a Transient VLP Production in a Stirred-Tank Bioreactor
3.3. Monitoring a Transient VLP Production in a Stirred-Tank Bioreactor Using Dielectric Spectroscopy
3.4. Characterization of Produced YF-VLPs
4. Discussion
4.1. Impact of Various Parameters on pDNA Production in E. coli
4.2. Influence of Different Process Parameters on Transient Transfection
4.3. Implementation of Dielectric Spectroscopy into a Transient YF-VLP Production Process
4.4. Characterization of the YF-VLP
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Appendix A
References
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Standard | 8 | 6 | 5 | 1 | 7 | 3 | 4 | 12 | 11 | 9 | 10 | 2 | Center Point | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Run | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | 16 | 17 | 18 | 19 | 20 |
LB | 1 | −1 | −1 | 1 | 1 | 1 | −1 | −1 | 1 | 1 | −1 | −1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Meat-peptone | 1 | −1 | −1 | 1 | −1 | −1 | 1 | −1 | −1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Casein-peptone | −1 | −1 | 1 | −1 | −1 | 1 | −1 | −1 | 1 | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Yeast extract | −1 | 1 | −1 | 1 | −1 | 1 | 1 | −1 | 1 | −1 | 1 | −1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Glucose | −1 | −1 | 1 | 1 | 1 | −1 | 1 | −1 | 1 | −1 | −1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Glycerol | 1 | 1 | 1 | 1 | −1 | 1 | −1 | −1 | −1 | −1 | −1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Phosphate * | −1 | 1 | −1 | −1 | 1 | 1 | 1 | −1 | −1 | 1 | −1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
NaCl | 1 | −1 | 1 | −1 | 1 | 1 | 1 | −1 | −1 | −1 | 1 | −1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
MgSO4 | 1 | 1 | 1 | −1 | −1 | −1 | 1 | −1 | 1 | 1 | −1 | −1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Dummy 1 | −1 | 1 | 1 | 1 | 1 | −1 | −1 | −1 | −1 | 1 | 1 | −1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Dummy 2 | 1 | 1 | −1 | −1 | 1 | −1 | −1 | −1 | 1 | −1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
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Dekevic, G.; Tertel, T.; Tasto, L.; Schmidt, D.; Giebel, B.; Czermak, P.; Salzig, D. A Bioreactor-Based Yellow Fever Virus-like Particle Production Process with Integrated Process Analytical Technology Based on Transient Transfection. Viruses 2023, 15, 2013. https://doi.org/10.3390/v15102013
Dekevic G, Tertel T, Tasto L, Schmidt D, Giebel B, Czermak P, Salzig D. A Bioreactor-Based Yellow Fever Virus-like Particle Production Process with Integrated Process Analytical Technology Based on Transient Transfection. Viruses. 2023; 15(10):2013. https://doi.org/10.3390/v15102013
Chicago/Turabian StyleDekevic, Gregor, Tobias Tertel, Lars Tasto, Deborah Schmidt, Bernd Giebel, Peter Czermak, and Denise Salzig. 2023. "A Bioreactor-Based Yellow Fever Virus-like Particle Production Process with Integrated Process Analytical Technology Based on Transient Transfection" Viruses 15, no. 10: 2013. https://doi.org/10.3390/v15102013
APA StyleDekevic, G., Tertel, T., Tasto, L., Schmidt, D., Giebel, B., Czermak, P., & Salzig, D. (2023). A Bioreactor-Based Yellow Fever Virus-like Particle Production Process with Integrated Process Analytical Technology Based on Transient Transfection. Viruses, 15(10), 2013. https://doi.org/10.3390/v15102013