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Title: Modeling of copy number variability in Pichia pastoris
Abstract

Development of continuous biopharmaceutical manufacturing processes is an area of active research. This study considers the long‐term transgene copy number stability ofPichia pastorisin 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 ofPichia pastorisand the resultant products.

 
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NSF-PAR ID:
10361401
Author(s) / Creator(s):
 ;  ;  ;  ;  ;  ;  
Publisher / Repository:
Wiley Blackwell (John Wiley & Sons)
Date Published:
Journal Name:
Biotechnology and Bioengineering
Volume:
118
Issue:
5
ISSN:
0006-3592
Page Range / eLocation ID:
p. 1832-1839
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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