PVX-tolerant potato development using a nucleic acid-hydrolyzing recombinant antibody

Yang, J.-G.; Hwang, Kyongmin; Kil, Eui-Joon; Park, J.; Cho, S.; Lee, Y.-G.; Auh, Chung-Kyoon; Rhee, Yong; Lee, S.

doi:10.4149/av_2017_01_105

Cited by 3 publications

(3 citation statements)

References 41 publications

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“…The advantages of producing scFv forms that can be generated in a single chain have long attracted attention in the eld of biologics, particularly plant-based biotechnology 25 . In addition to scFv antibodies against plant pathogens, scFvs against botulinum neurotoxin A (BoNT/A), human epidermal growth factor receptor 1 (HER1), HER2, and Gibberlin have been produced in live N. Ventamiana, N. tabacum, and A. thaliana, among other plants 26,27 . However, none of the plant-derived scFvs developed as vaccines, targeted anticancer drugs, or antidotes have advanced to clinical trials.…”

Section: Discussionmentioning

confidence: 99%

Nicotiana benthamiana-derived dupilumab-scFv reaches deep into the cultured human nasal epithelial cells and inhibits CCL26 expression

Kwon,

Cho,

Ahn

et al. 2024

Preprint

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Plants offer a cost-effective and scalable pharmaceutical platform devoid of host-derived contamination risks. However, their medical application is complicated by the potential for acute allergic reactions to external proteins. Developing plant-based protein therapeutics for localized diseases with non-invasive treatment modalities may capitalize on the benefits of plant proteins while avoiding their inherent risks. Dupilumab, which is effective against a variety of allergic and autoimmune diseases but has systemic responses and injection-related side effects, may be more beneficial if delivered locally using a small biological form. In this study, we engineered a single-chain variable fragment (scFv) of dupilumab, termed Dup-scFv produced by Nicotiana benthamiana, and evaluated its tissue permeability and anti-inflammatory efficacy in air-liquid interface cultured human nasal epithelial cells. Despite showing 3.67- and 17-fold lower binding affinity for IL-4Ra in surface plasmon resonance assays and cell binding assays, respectively, Dup-scFv retained most of the affinity of dupilumab, which was originally high, with a dissociation constant (KD) of 4.76 pM. In human nasal epithelial cells cultured at the air-liquid interface, Dup-scFv administered on the air side inhibited the inflammatory marker CCL26 in hard-to-reach basal cells more effectively than dupilumab. In addition, Dup-scFv had an overall permeability of 0.8% across cell layers compared to undetectable levels of dupilumab. These findings suggest that plant-produced Dup-scFv can be delivered non-invasively to cultured human nasal epithelial cells to alleviate inflammatory signaling, providing a practical approach to utilize plant-based proteins for topical therapeutic applications.

show abstract

Section: Discussionmentioning

confidence: 99%

Nicotiana benthamiana-derived dupilumab-scFv reaches deep into the cultured human nasal epithelial cells and inhibits CCL26 expression

Kwon,

Cho,

Ahn

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…The advantages of producing scFv forms that can be generated in a single chain have long attracted attention in the field of biologics, particularly plant-based biotechnology 24 . In addition to scFv antibodies against plant pathogens, scFvs against botulinum neurotoxin A (BoNT/A), human epidermal growth factor receptor 1 (HER1), HER2, and Gibberlin (a peptide hormone inhibiting appetite) have been produced in live N. Benthamiana , N. tabacum , and A. thaliana , among other plants 25 , 26 . However, none of the plant-derived scFvs developed as vaccines, targeted anticancer drugs, or antidotes have advanced to clinical trials.…”

Section: Discussionmentioning

confidence: 99%

Nicotiana benthamiana-derived dupilumab-scFv reaches deep into the cultured human nasal epithelial cells and inhibits CCL26 expression

Kwon,

Cho,

Ahn

et al. 2024

Sci Rep

View full text Add to dashboard Cite

Plants offer a cost-effective and scalable pharmaceutical platform devoid of host-derived contamination risks. However, their medical application is complicated by the potential for acute allergic reactions to external proteins. Developing plant-based protein therapeutics for localized diseases with non-invasive treatment modalities may capitalize on the benefits of plant proteins while avoiding their inherent risks. Dupilumab, which is effective against a variety of allergic and autoimmune diseases but has systemic responses and injection-related side effects, may be more beneficial if delivered locally using a small biological form. In this study, we engineered a single-chain variable fragment (scFv) of dupilumab, termed Dup-scFv produced by Nicotiana benthamiana, and evaluated its tissue permeability and anti-inflammatory efficacy in air–liquid interface cultured human nasal epithelial cells (HNECs). Despite showing 3.67- and 17-fold lower binding affinity for IL-4Ra in surface plasmon resonance assays and cell binding assays, respectively, Dup-scFv retained most of the affinity of dupilumab, which was originally high, with a dissociation constant (KD) of 4.76 pM. In HNECs cultured at the air–liquid interface, Dup-scFv administered on the air side inhibited the inflammatory marker CCL26 in hard-to-reach basal cells more effectively than dupilumab. In addition, Dup-scFv had an overall permeability of 0.8% across cell layers compared to undetectable levels of dupilumab. These findings suggest that plant-produced Dup-scFv can be delivered non-invasively to cultured HNESc to alleviate inflammatory signaling, providing a practical approach to utilize plant-based proteins for topical therapeutic applications.

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“…Well-characterized in vitro propagation, transformation, and maintenance methods of these plants are the factors behind their selection. The protein was expressed in whole plant tissue [66,68,69], leaves [70][71][72][73][74][75], flower [76], seeds [77][78][79][80][81], hairy root culture [82] or tobacco BY-2 (tobacco cultivar Bright Yellow) cells [8,83,84] (Fig. 4).…”

Section: Transformation Methodologies Target Plants and Expression Omentioning

confidence: 99%

Expression of Single Chain Variable Fragment (scFv) Molecules in Plants: A Comprehensive Update

Satheeshkumar

2020

Mol Biotechnol

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Single chain variable fragments (scFvs) are generated by joining together the variable heavy and light chain of a monoclonal antibody (mAb) via a peptide linker. They offer some advantages over the parental mAb such as low molecular weight, heterologous production, multimeric form, and multivalency. The scFvs were produced against more than 50 antigens till date using 10 different plant species as the expression system. There were considerable improvements in the expression and purification strategies of scFv in the last 24 years. With the growing demand of scFv in therapeutic and diagnostic fields, its biosynthesis needs to be increased. The easiness in development, maintenance, and multiplication of transgenic plants make them an attractive expression platform for scFv production. The review intends to provide comprehensive information about the use of plant expression system to produce scFv. The developments, advantages, pitfalls, and possible prospects of improvement for the exploitation of plants in the industrial level are discussed.

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PVX-tolerant potato development using a nucleic acid-hydrolyzing recombinant antibody

Cited by 3 publications

References 41 publications

Nicotiana benthamiana-derived dupilumab-scFv reaches deep into the cultured human nasal epithelial cells and inhibits CCL26 expression

Nicotiana benthamiana-derived dupilumab-scFv reaches deep into the cultured human nasal epithelial cells and inhibits CCL26 expression

Nicotiana benthamiana-derived dupilumab-scFv reaches deep into the cultured human nasal epithelial cells and inhibits CCL26 expression

Expression of Single Chain Variable Fragment (scFv) Molecules in Plants: A Comprehensive Update

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