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Review
. 2019 Dec 20:7:420.
doi: 10.3389/fbioe.2019.00420. eCollection 2019.

Recent Developments in Bioprocessing of Recombinant Proteins: Expression Hosts and Process Development

Nagesh K Tripathi  1 , Ambuj Shrivastava  2
Affiliations
Review

Recent Developments in Bioprocessing of Recombinant Proteins: Expression Hosts and Process Development

Nagesh K Tripathi et al. Front Bioeng Biotechnol. .

Abstract

Infectious diseases, along with cancers, are among the main causes of death among humans worldwide. The production of therapeutic proteins for treating diseases at large scale for millions of individuals is one of the essential needs of mankind. Recent progress in the area of recombinant DNA technologies has paved the way to producing recombinant proteins that can be used as therapeutics, vaccines, and diagnostic reagents. Recombinant proteins for these applications are mainly produced using prokaryotic and eukaryotic expression host systems such as mammalian cells, bacteria, yeast, insect cells, and transgenic plants at laboratory scale as well as in large-scale settings. The development of efficient bioprocessing strategies is crucial for industrial production of recombinant proteins of therapeutic and prophylactic importance. Recently, advances have been made in the various areas of bioprocessing and are being utilized to develop effective processes for producing recombinant proteins. These include the use of high-throughput devices for effective bioprocess optimization and of disposable systems, continuous upstream processing, continuous chromatography, integrated continuous bioprocessing, Quality by Design, and process analytical technologies to achieve quality product with higher yield. This review summarizes recent developments in the bioprocessing of recombinant proteins, including in various expression systems, bioprocess development, and the upstream and downstream processing of recombinant proteins.

Keywords: continuous chromatography; downstream processing; high-throughput technology; integrated continuous bioprocessing; perfusion cell culture; process development; protein expression; upstream processing.

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Figures

Figure 1
Figure 1
Flow chart of the production of therapeutic monoclonal antibody using mammalian cell culture.
Figure 2
Figure 2
Flow chart of the purification of recombinant proteins expressed as IBs using E. coli.
Figure 3
Figure 3
Flow chart of the purification of extracellular and periplasmic space-expressed recombinant proteins.
Figure 4
Figure 4
Flow chart of the different technologies within continuous bioprocessing.
See this image and copyright information in PMC

References

    1. Agbogbo F. K., Ecker D. M., Farrand A., Han K., Khoury A., Martin A., et al. (2019). Current perspectives on biosimilars. J. Ind. Microbiol. Biotechnol. 46, 1297–1311. 10.1007/s10295-019-02216-z - DOI - PMC - PubMed
    1. Aguilar P. P., González-Domínguez I., Schneider T. A., Gòdia F., Cervera L., Jungbauer A. (2019). At-line multi-angle light scattering detector for faster process development in enveloped virus-like particle purification. J. Sep. Sci. 42, 2640–2649. 10.1002/jssc.201900441 - DOI - PMC - PubMed
    1. Ahmad M., Hirz M., Pichler H., Schwab H. (2014). Protein expression in Pichia pastoris: recent achievements and perspectives for heterologous protein production. Appl. Microbiol. Biotechnol. 98, 5301–5317. 10.1007/s00253-014-5732-5 - DOI - PMC - PubMed
    1. Ali A. S., Raju R., Kshirsagar R., Ivanov A. R., Gilbert A., Zang L., et al. (2019). Multi-omics study on the impact of cysteine feed level on cell viability and mAb production in a CHO bioprocess. Biotechnol. J. 14, 1800352. 10.1002/biot.201800352 - DOI - PubMed
    1. Amann T., Schmieder V., Faustrup Kildegaard H., Borth N., Andersen M. R. (2019). Genetic engineering approaches to improve posttranslational modification of biopharmaceuticals in different production platforms. Biotechnol. Bioeng. 116, 2778–2796. 10.1002/bit.27101 - DOI - PubMed

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