Plant‐Produced Antibodies and Post‐Translational Modification

Loos, Andreas; Steinkellner, Herta

doi:10.1002/9781118801512.ch9

Cited by 2 publications

(4 citation statements)

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“…Plants have proven to be versatile production systems for the expression and assembly of heavy and light chains of functional antibodies. These include full-sized and chimeric IgG, IgA, IgE, Ig fragments (ScFv and Fab), and even complex molecules such as pentameric and hexameric IgMs (Loos and Steinkellner, 2018;Komarova et al, 2019). However, some reports on the expression of antibodies and antibody fragments in plants indicate that there are challenges regarding expression, subcellular localization, and proteolytic degradation.…”

Section: Discussionmentioning

confidence: 99%

The Instability of Dimeric Fc-Fusions Expressed in Plants Can Be Solved by Monomeric Fc Technology

et al. 2021

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The potential therapeutic value of many proteins is ultimately limited by their rapid in vivo clearance. One strategy to limit clearance by metabolism and excretion, and improving the stability of therapeutic proteins, is their fusion to the immunoglobulin fragment crystallizable region (Fc). The Fc region plays multiple roles in (i) dimerization for the formation of “Y”-shaped structure of Ig, (ii) Fc-mediated effector functions, (iii) extension of serum half-life, and (iv) a cost-effective purification tag. Plants and in particular Nicotiana benthamiana have proven to be suitable expression platforms for several recombinant therapeutic proteins. Despite the enormous success of their use for the production of full-length monoclonal antibodies, the expression of Fc-fused therapeutic proteins in plants has shown limitations. Many Fc-fusion proteins expressed in plants show different degrees of instability resulting in high amounts of Fc-derived degradation products. To address this issue, we used erythropoietin (EPO) as a reporter protein and evaluated the efforts to enhance the expression of full-length EPO-Fc targeted to the apoplast of N. benthamiana. Our results show that the instability of the fusion protein is independent from the Fc origin or IgG subclass and from the peptide sequence used to link the two domains. We also show that a similar instability occurs upon the expression of individual heavy chains of monoclonal antibodies and ScFv-Fc that mimic the “Y”-shape of antibodies but lack the light chain. We propose that in this configuration, steric hindrance between the protein domains leads to physical instability. Indeed, mutations of critical residues located on the Fc dimerization interface allowed the expression of fully stable EPO monomeric Fc-fusion proteins. We discuss the limitations of Fc-fusion technology in N. benthamiana transient expression systems and suggest strategies to optimize the Fc-based scaffolds on their folding and aggregation resistance in order to improve the stability.

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Section: Discussionmentioning

confidence: 99%

The Instability of Dimeric Fc-Fusions Expressed in Plants Can Be Solved by Monomeric Fc Technology

et al. 2021

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“…[ 35 ] Indeed, these advantages, combined with PTMs' potential by molecular farming, can represent numerous opportunities for the pharmaceutical market. [ 32,33 ]…”

Section: Plant Molecular Factories: Amp Productionmentioning

confidence: 99%

“…The targeted synthesis can be a strategy to improve the activity of molecules such as promoting the stability of PTMs. [33,34] The plant cell is capable to promote the efficient folding of the complex proteins and also improving the stability of recombinant proteins. [35] The PTM is a crucial event in human molecule production.…”

Section: Plant Molecular Factories: Amp Productionmentioning

confidence: 99%

“…[35] Indeed, these advantages, combined with PTMs' potential by molecular farming, can represent numerous opportunities for the pharmaceutical market. [32,33] Currently, it is possible to obtain field or lab-grown transgenic plants that store homologous and/or heterologous molecules, which improve the defense and nutritional value of plants and produce molecules with therapeutic interest including AMPs. [32,36] It can, thus, be possible to overcome the challenges presented by other expression systems of heterologous AMPs.…”

Section: Plant Molecular Factories: Amp Productionmentioning

confidence: 99%

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Advances in the use of plants as potential biofactories in the production of antimicrobial peptides

Santos

Franco

2022

Peptide Science

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Plants subjected to phytopathogens can synthesize peptides with antimicrobial properties. In the last few decades, there has been an impressive increase in the prospection of antimicrobial peptides (AMPs) due to continuous demand for the development and manufacture of new antibiotics. In this setting, plants have attracted scientific and pharmaceutical interest and are considered promising AMPs biofactories. However, it is a great challenge to explore the diversity of actions needed to obtain a pharmaceutical product with AMPs derived from plants on a large scale. This review presents the last 5 years main findings on plants used as AMPs biofactories. Published works in this period were reviewed, and perspectives are presented on recombinant AMPs for drug production that appear in a plant-based system, as well as products available on the market.

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Plant‐Produced Antibodies and Post‐Translational Modification

Cited by 2 publications

References 44 publications

The Instability of Dimeric Fc-Fusions Expressed in Plants Can Be Solved by Monomeric Fc Technology

The Instability of Dimeric Fc-Fusions Expressed in Plants Can Be Solved by Monomeric Fc Technology

Advances in the use of plants as potential biofactories in the production of antimicrobial peptides

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