Modeling of copy number variability in Pichia pastoris
Development of continuous biopharmaceutical manufacturing processes is an area of active research. This study considers the long-term transgene copy number stability of Pichia pastoris in continuous bioreactors. We propose a model of copy number loss that quantifies population heterogeneity. An anal...
| Main Authors: | , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022
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| Online Access: | https://hdl.handle.net/1721.1/140439 |
| _version_ | 1826212254206394368 |
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| author | Lu, Amos E. Maloney, Andrew J. Dalvie, Neil C. Brady, Joseph R. Love, Kerry R. Love, J. Christopher Braatz, Richard D. |
| author2 | Massachusetts Institute of Technology. Department of Chemical Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Chemical Engineering Lu, Amos E. Maloney, Andrew J. Dalvie, Neil C. Brady, Joseph R. Love, Kerry R. Love, J. Christopher Braatz, Richard D. |
| author_sort | Lu, Amos E. |
| collection | MIT |
| description | Development of continuous biopharmaceutical manufacturing processes is an area of active research. This study considers the long-term transgene copy number stability of Pichia pastoris in continuous bioreactors. We propose a model of copy number loss that quantifies population heterogeneity. An analytical solution is derived and compared with existing experimental data. The model is then used to provide guidance for stable operating timescales. The model is extended to consider copy number dependent growth such as in the case of Zeocin supplementation. The model is also extended to analyze a continuous seeding strategy. This study is a critical step towards understanding the impact of continuous processing on the stability of Pichia pastoris and the resultant products. |
| first_indexed | 2024-09-23T15:18:46Z |
| format | Article |
| id | mit-1721.1/140439 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T15:18:46Z |
| publishDate | 2022 |
| publisher | Wiley |
| record_format | dspace |
| spelling | mit-1721.1/1404392024-06-06T20:10:48Z Modeling of copy number variability in Pichia pastoris Lu, Amos E. Maloney, Andrew J. Dalvie, Neil C. Brady, Joseph R. Love, Kerry R. Love, J. Christopher Braatz, Richard D. Massachusetts Institute of Technology. Department of Chemical Engineering Koch Institute for Integrative Cancer Research at MIT Development of continuous biopharmaceutical manufacturing processes is an area of active research. This study considers the long-term transgene copy number stability of Pichia pastoris in continuous bioreactors. We propose a model of copy number loss that quantifies population heterogeneity. An analytical solution is derived and compared with existing experimental data. The model is then used to provide guidance for stable operating timescales. The model is extended to consider copy number dependent growth such as in the case of Zeocin supplementation. The model is also extended to analyze a continuous seeding strategy. This study is a critical step towards understanding the impact of continuous processing on the stability of Pichia pastoris and the resultant products. 2022-02-16T19:04:32Z 2022-02-16T19:04:32Z 2021-02-02 Article http://purl.org/eprint/type/JournalArticle 0006-3592 1097-0290 https://hdl.handle.net/1721.1/140439 Lu, A. E., Maloney, A. J., Dalvie, N. C., et al. Modeling of copy number variability in Pichia pastoris. Biotechnology and Bioengineering. 2021; 118: 1832– 1839. en http://dx.doi.org/10.1002/bit.27698 Biotechnology and Bioengineering Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Wiley Wiley |
| spellingShingle | Lu, Amos E. Maloney, Andrew J. Dalvie, Neil C. Brady, Joseph R. Love, Kerry R. Love, J. Christopher Braatz, Richard D. Modeling of copy number variability in Pichia pastoris |
| title | Modeling of copy number variability in Pichia pastoris |
| title_full | Modeling of copy number variability in Pichia pastoris |
| title_fullStr | Modeling of copy number variability in Pichia pastoris |
| title_full_unstemmed | Modeling of copy number variability in Pichia pastoris |
| title_short | Modeling of copy number variability in Pichia pastoris |
| title_sort | modeling of copy number variability in pichia pastoris |
| url | https://hdl.handle.net/1721.1/140439 |
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