RT Journal Article
SR Electronic
T1 A metabolic network-based approach for developing feeding strategies for CHO cells to increase monoclonal antibody production
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 751347
DO 10.1101/751347
A1 Hamideh Fouladiha
A1 Sayed-Amir Marashi
A1 Fatemeh Torkashvand
A1 Fereidoun Mahboudi
A1 Nathan E. Lewis
A1 Behrouz Vaziri
YR 2019
UL http://biorxiv.org/content/early/2019/09/01/751347.abstract
AB Background Chinese hamster ovary (CHO) cells are the main workhorse in the biopharmaceutical industry for the production of recombinant proteins, such as monoclonal antibodies. To date, a variety of metabolic engineering approaches have been used to improve the productivity of CHO cells. While genetic manipulations are potentially laborious cell line development and validation in mammalian cells, rational design of CHO cell culture medium or efficient fed-batch strategies are more popular metabolic engineering approaches.Results In this study, a genome-scale metabolic network model of CHO cells was used to design feeding strategies for CHO cells to improve monoclonal antibody (mAb) production. A number of metabolites, including threonine and arachidonate, were suggested by the model to be added into cell culture medium. The designed composition has been experimentally validated, and then optimized, using design of experiment methods. About a two-fold increase in the total mAb expression has been observed using this strategy.Conclusions Our approach can be used in similar metabolic engineering problems, in order to suggest new ways of increasing production in different cell factories.