Academic Journal
Non-invasive strategy: Developing a topical IL-4Rα-specific nanobody for the treatment of allergic airway diseases
| Title: | Non-invasive strategy: Developing a topical IL-4Rα-specific nanobody for the treatment of allergic airway diseases |
|---|---|
| Authors: | Taeyoung Ahn, Dong Hyuk Lee, GeunAh Kim, JiHyun Kim, Joon-Sang Park, Hyung-Ju Cho, Joo Young Kim |
| Source: | Materials Today Bio, Vol 27, Iss , Pp 101148- (2024) |
| Publisher Information: | Elsevier, 2024. |
| Publication Year: | 2024 |
| Collection: | LCC:Medicine (General) LCC:Biology (General) |
| Subject Terms: | Allergic rhinitis, Interleukin-4 receptor α, Nanobody, In-silico affinity maturation, Non-invasive treatment, Medicine (General), R5-920, Biology (General), QH301-705.5 |
| More Details: | Inhibiting IL-4 and IL-13 are critical cytokines that induce the pathogenic responses of allergic airway diseases. Currently, monoclonal antibodies targeting IL-4Rα are administered subcutaneously to treat eosinophilic rhinosinusitis and allergic asthma. However, these treatments have several drawbacks. To address these issues, we have developed a novel IL-4Rα-targeting nanobody designed for non-invasive delivery to local inflammatory sites in allergic airway diseases. H5, selected via the ribosomal display applied screening from synthetic nanobody library, underwent dimerization and in-silico affinity maturation using AlphaFold2 and GROMACS resulting in a substantial/dramatic enhancement of its binding affinity. H5 effectively controlled inflammatory markers such as MUC5AC, CCL26, and FOXJ1 in human nasal epithelial cells (HNECs) by inhibiting IL-4 and IL-13 signaling. The bivalent form of H5 showed efficacy in easily accessible cells, such as multi-ciliated cells, while the monovalent variant targeted hard-to-reach cells, such as basal cells of HNECs. In summary, we developed a nanobody that could effectively inhibit inflammatory signaling in HNECs via intranasal administration, showing promise as a non-invasive rhinitis treatment. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2590-0064 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2590006424002072; https://doaj.org/toc/2590-0064 |
| DOI: | 10.1016/j.mtbio.2024.101148 |
| Access URL: | https://doaj.org/article/f465aa55d3fd4613a27ed8513b7aacb9 |
| Accession Number: | edsdoj.f465aa55d3fd4613a27ed8513b7aacb9 |
| Database: | Directory of Open Access Journals |
| ISSN: | 25900064 |
|---|---|
| DOI: | 10.1016/j.mtbio.2024.101148 |
| Published in: | Materials Today Bio |
| Language: | English |