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Comparison of Multi-Objective Evolutionary Algorithms to Solve the Modular Cell Design Problem for Novel Biocatalysis

Key Challenges in Designing CHO Chassis Platforms

Centro de Engenharia Biológica, Universidade do Minho, 4710-057 Braga, Portugal
Acib GmbH– Austrian Centre of Industrial Biotechnology, 1190 Vienna, Austria
Department of Biotechnology, BOKU University of Natural Resources and Life Sciences, 1190 Vienna, Austria
ITQB-NOVA, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, 2780-157 Oeiras, Portugal
Department of Analytical Chemistry, University of Vienna, 1090 Vienna, Austria
Author to whom correspondence should be addressed.
Both authors contributed equally.
Processes 2020, 8(6), 643;
Received: 31 March 2020 / Revised: 22 May 2020 / Accepted: 25 May 2020 / Published: 28 May 2020
(This article belongs to the Collection Principles of Modular Design and Control in Complex Systems)
Following the success of and the high demand for recombinant protein-based therapeutics during the last 25 years, the pharmaceutical industry has invested significantly in the development of novel treatments based on biologics. Mammalian cells are the major production systems for these complex biopharmaceuticals, with Chinese hamster ovary (CHO) cell lines as the most important players. Over the years, various engineering strategies and modeling approaches have been used to improve microbial production platforms, such as bacteria and yeasts, as well as to create pre-optimized chassis host strains. However, the complexity of mammalian cells curtailed the optimization of these host cells by metabolic engineering. Most of the improvements of titer and productivity were achieved by media optimization and large-scale screening of producer clones. The advances made in recent years now open the door to again consider the potential application of systems biology approaches and metabolic engineering also to CHO. The availability of a reference genome sequence, genome-scale metabolic models and the growing number of various “omics” datasets can help overcome the complexity of CHO cells and support design strategies to boost their production performance. Modular design approaches applied to engineer industrially relevant cell lines have evolved to reduce the time and effort needed for the generation of new producer cells and to allow the achievement of desired product titers and quality. Nevertheless, important steps to enable the design of a chassis platform similar to those in use in the microbial world are still missing. In this review, we highlight the importance of mammalian cellular platforms for the production of biopharmaceuticals and compare them to microbial platforms, with an emphasis on describing novel approaches and discussing still open questions that need to be resolved to reach the objective of designing enhanced modular chassis CHO cell lines. View Full-Text
Keywords: Chinese Hamster Ovary (CHO); systems metabolic engineering; recombinant proteins; chassis cell; modularity Chinese Hamster Ovary (CHO); systems metabolic engineering; recombinant proteins; chassis cell; modularity
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MDPI and ACS Style

Hamdi, A.; Széliová, D.; Ruckerbauer, D.E.; Rocha, I.; Borth, N.; Zanghellini, J. Key Challenges in Designing CHO Chassis Platforms. Processes 2020, 8, 643.

AMA Style

Hamdi A, Széliová D, Ruckerbauer DE, Rocha I, Borth N, Zanghellini J. Key Challenges in Designing CHO Chassis Platforms. Processes. 2020; 8(6):643.

Chicago/Turabian Style

Hamdi, Anis, Diana Széliová, David E. Ruckerbauer, Isabel Rocha, Nicole Borth, and Jürgen Zanghellini. 2020. "Key Challenges in Designing CHO Chassis Platforms" Processes 8, no. 6: 643.

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