| Autor: |
Marzia Martina, Umberto Banderali, Alvaro Yogi, Mehdi Arbabi Ghahroudi, Hong Liu, Traian Sulea, Yves Durocher, Greg Hussack, Henk van Faassen, Balu Chakravarty, Qing Yan Liu, Umar Iqbal, Binbing Ling, Etienne Lessard, Joey Sheff, Anna Robotham, Debbie Callaghan, Maria Moreno, Tanya Comas, Dao Ly, Danica Stanimirovic |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Advanced Science, Vol 11, Iss 40, Pp n/a-n/a (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2198-3844 |
| DOI: |
10.1002/advs.202405432 |
| Popis: |
Abstract Genetic studies have identified the voltage‐gated sodium channel 1.7 (Nav1.7) as pain target. Due to the ineffectiveness of small molecules and monoclonal antibodies as therapeutics for pain, single‐domain antibodies (VHHs) are developed against the human Nav1.7 (hNav1.7) using a novel antigen presentation strategy. A 70 amino‐acid peptide from the hNav1.7 protein is identified as a target antigen. A recombinant version of this peptide is grafted into the complementarity determining region 3 (CDR3) loop of an inert VHH in order to maintain the native 3D conformation of the peptide. This antigen is used to isolate one VHH able to i) bind hNav1.7, ii) slow the deactivation of hNav1.7, iii) reduce the ability of eliciting action potentials in nociceptors, and iv) reverse hyperalgesia in in vivo rat and mouse models. This VHH exhibits the potential to be developed as a therapeutic capable of suppressing pain. This novel antigen presentation strategy can be applied to develop biologics against other difficult targets such as ion channels, transporters and GPCRs. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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