دورية أكاديمية
Nicotiana benthamiana-derived dupilumab-scFv reaches deep into the cultured human nasal epithelial cells and inhibits CCL26 expression
| العنوان: | Nicotiana benthamiana-derived dupilumab-scFv reaches deep into the cultured human nasal epithelial cells and inhibits CCL26 expression |
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| المؤلفون: | Beom Jun Kwon, Na Hyun Cho, Taeyoung Ahn, Geunah Kim, Nguyễn Thị Xuân Diệu, Woo Taek Kim, Hyung-Ju Cho, Dong Hye Seo, Joo Young Kim |
| المصدر: | Scientific Reports, Vol 14, Iss 1, Pp 1-10 (2024) |
| بيانات النشر: | Nature Portfolio, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | ScFv, Dupilumab, Nicotiana benthamiana, Human nasal epithelial cell, Non-invasive treatment, Medicine, Science |
| الوصف: | Abstract 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2045-2322 |
| Relation: | https://doaj.org/toc/2045-2322 |
| DOI: | 10.1038/s41598-024-65524-0 |
| URL الوصول: | https://doaj.org/article/511d5664a0bf456e8362af26456beb85 |
| رقم الأكسشن: | edsdoj.511d5664a0bf456e8362af26456beb85 |
| قاعدة البيانات: | Directory of Open Access Journals |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 20452322 |
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| DOI: | 10.1038/s41598-024-65524-0 |