Multi-scale design and optimization of antibody production via flexible nets
- Author(s)
- Jorge Lázaro, Teresa Joven, Diana Széliová, Jürgen Zanghellini, Jorge Júlvez
- Abstract
Antibodies are therapeutic proteins with many applications in medicine, such as treating viral infections, different types of cancer, and common diseases such as psoriasis and multiple sclerosis. Chinese Hamster Ovary (CHO) cells are the most widely used cells for antibody production due to their well-established use and favorable features. However, the current design of antibody production systems often relies on a “trial and error” approach to manipulate CHO cells. This approach is time-consuming and costly, and can lead to suboptimal process performance. The use of mathematical models has the potential to greatly accelerate and improve the design and optimization of antibody production. Starting from a systematic and formal approach, the aim is to achieve an automatic design of the whole process that allows optimal productivity to be reached. To this end, we develop mathematical models and methods for the design and optimization of antibody manufacturing systems. The mathematical models are based on Flexible Nets (FNs), a modeling formalism that accommodates uncertain parameters and nonlinear dynamics. FNs enable the development of comprehensive models that encompass both the metabolic network of CHO cells and the dynamics of the bioreactor in which the cells are cultured. Thus, by integrating macroscopic variables (e.g. dilution rate, substrate concentration, cell density, etc.) with microscopic variables (such as intracellular metabolic fluxes), our model represents a multi-scale system and facilitates global optimization.
- Organisation(s)
- Department of Analytical Chemistry
- External organisation(s)
- Universidad de Zaragoza
- Journal
- Computational and Structural Biotechnology Journal
- Volume
- 27
- Pages
- 1498-1510
- No. of pages
- 13
- ISSN
- 2001-0370
- DOI
- https://doi.org/10.1016/j.csbj.2025.03.040
- Publication date
- 01-2025
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 104027 Computational chemistry, 106005 Bioinformatics, 301303 Medical biochemistry
- Keywords
- ASJC Scopus subject areas
- Biotechnology, Biophysics, Structural Biology, Biochemistry, Genetics, Computer Science Applications
- Sustainable Development Goals
- SDG 3 - Good Health and Well-being
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/c6fdb57e-8b30-48a1-a3a2-a36a2a9470a6