Towards high-yield production of pharmaceutical proteins with plant cell suspension cultures

Xu, Jianfeng; Ge, Xinna; Dolan, Maureen C.

doi:10.1016/j.biotechadv.2011.01.002

Cited by 188 publications

(164 citation statements)

References 297 publications

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“…Under special cultivation conditions in simple synthetic liquid media using conventional bioreactors, undifferentiated plant cells can be separated and propagated as specialized factories for the production of secondary metabolites and, more recently, human-like therapeutic proteins (Xu et al, 2011).…”

Section: Expression Systems For Recombinant Protein Productionmentioning

confidence: 99%

Review Soybeans as bioreactors for biopharmaceuticals and industrial proteins

Vianna¹,

Cunha²,

Murad³

et al. 2011

Genet. Mol. Res.

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Section: Expression Systems For Recombinant Protein Productionmentioning

confidence: 99%

Review Soybeans as bioreactors for biopharmaceuticals and industrial proteins

Vianna¹,

Cunha²,

Murad³

et al. 2011

Genet. Mol. Res.

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“…It is estimated that there are about 150 protein-based drugs on the market with sales exceeding $100 billion per year. 1 Notable successes include the design and development of insulin formulations of varying durations, and more recently, the development and application of a wide variety of novel anticancer therapeutics including monoclonal antibodies (mAbs). There are currently over 30 mAb based drugs approved for commercial use with hundreds more in clinical trials.…”

Section: Introductionmentioning

confidence: 99%

Probing structurally altered and aggregated states of therapeutically relevant proteins using GroEL coupled to bio‐layer interferometry

et al. 2014

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The ability of a GroEL-based bio-layer interferometry (BLI) assay to detect structurally altered and/or aggregated species of pharmaceutically relevant proteins is demonstrated. Assay development included optimizing biotinylated-GroEL immobilization to streptavidin biosensors, combined with biophysical and activity measurements showing native and biotinylated GroEL are both stable and active. First, acidic fibroblast growth factor (FGF-1) was incubated under conditions known to promote (40 C) and inhibit (heparin addition) molten globule formation. Heat exposed (40 C) FGF-1 exhibited binding to GroEL-biosensors, which was significantly diminished in the presence of heparin. Second, a polyclonal human IgG solution containing 6-8% non-native dimer showed an increase in higher molecular weight aggregates upon heating by size exclusion chromatography (SEC). The poly IgG solution displayed binding to GroEL-biosensors initially with progressively increased binding upon heating. Enriched preparations of the IgG dimers or monomers showed significant binding to GroEL-biosensors. Finally, a thermally treated IgG1 monoclonal antibody (mAb) solution also demonstrated increased GroEL-biosensor binding, but with different Additional Supporting Information may be found in the online version of this article. Subhashchandra Naik and Ozan S. Kumru contributed equally to the work. kinetics. The bound complexes could be partially to fully dissociated after ATP addition (i.e., specific GroEL binding) depending on the protein, environmental stress, and the assay's experimental conditions. Transmission electron microscopy (TEM) images of GroEL-mAb complexes, released from the biosensor, also confirmed interaction of bound complexes at the GroEL binding site with heat-stressed mAb. Results indicate that the GroEL-biosensor-BLI method can detect conformationally altered and/or early aggregation states of proteins, and may potentially be useful as a rapid, stability-indicating biosensor assay for monitoring the structural integrity and physical stability of therapeutic protein candidates.

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“…Attention has been focused on plants as a protein factory, because the plant system is low in cost, lacks animal pathogens, and capable of posttranslational modifications (Xu et al 2011). Suspensioncultured plant cells have been traditionally used for the production of plant-derived natural compounds.…”

mentioning

confidence: 99%

“…Thus, pharmaceutical protein production has been attempted in suspension-cultured plant cells (Basaran and Rodríguez-Cerezo 2008;Karg and Kallio 2009;Hellwing et al 2004). Compared with whole plants, the plant cell culture system has some advantages, such as inexpensive chemicals for their culture, controllable culture conditions, and reproducible environmental parameters (Xu et al 2011). These advantages allow suspensioncultured cells to meet the regulatory requirements for the production of pharmaceutical proteins and to work as an environmentally friendly bioreactor.…”

mentioning

confidence: 99%

“…Although Xu et al (2011) reviewed the improvement of the medium and process to increase the production of recombinant proteins in plant cells, no study of the control of N-glycosylation has yet been reported. Monosaccharide in the culture medium is a key factor in altering the N-glycosylation profile of endogenous or secreted proteins (Becerra-Arteaga and Shuler 2007).…”

mentioning

confidence: 99%

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<i>N</i>-Glycan structures of glycoproteins in suspension-cultured <i>Arabidopsis thaliana</i> T87 cells

Kajiura

Tanaka

Kato

et al. 2012

Plant Biotechnology

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Suspension-cultured plant cells are feasible bioreactors for the production of pharmaceutical proteins. Posttranslational modification, such as glycosylation, is important for in vivo biological and physiological roles of proteins. However, little is known about the effect of suspension-culture conditions on protein N-glycosylation. In this study, we studied the N-glycan structures of soluble and endogenous glycoproteins at different growth stages of suspension-cultured Arabidopsis thaliana T87 cells. At the late growth stage, the amount of N-glycans with terminal N-acetylglucosamine (GlcNAc) decreased, whereas that of N-glycans with fucose and xylose increased. This indicates that N-glycans have more plant-specific sugar residues as the cultivation reaches the late or end stage of plant growth.

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Towards high-yield production of pharmaceutical proteins with plant cell suspension cultures

Cited by 188 publications

References 297 publications

Review Soybeans as bioreactors for biopharmaceuticals and industrial proteins

Review Soybeans as bioreactors for biopharmaceuticals and industrial proteins

Probing structurally altered and aggregated states of therapeutically relevant proteins using GroEL coupled to bio‐layer interferometry

<i>N</i>-Glycan structures of glycoproteins in suspension-cultured <i>Arabidopsis thaliana</i> T87 cells

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