| Téléchargement | - Voir la version finale : A novel antigen design strategy to isolate single‐domain antibodies that target human Naᵥ1.7 and reduce pain in animal models (PDF, 7.7 Mio)
|
|---|
| DOI | Trouver le DOI : https://doi.org/10.1002/advs.202405432 |
|---|
| Auteur | Rechercher : Martina, Marzia1Identifiant ORCID : https://orcid.org/0009-0008-9732-6483; Rechercher : Banderali, Umberto1Identifiant ORCID : https://orcid.org/0000-0003-4034-0782; Rechercher : Yogi, Alvaro1; Rechercher : Arbabi Ghahroudi, Mehdi1Identifiant ORCID : https://orcid.org/0000-0002-8580-6083; Rechercher : Liu, Hong1; Rechercher : Sulea, Traian1Identifiant ORCID : https://orcid.org/0000-0001-5301-8261; Rechercher : Durocher, Yves1Identifiant ORCID : https://orcid.org/0000-0002-2268-4111; Rechercher : Hussack, Greg1Identifiant ORCID : https://orcid.org/0000-0002-9852-6865; Rechercher : van Faassen, Henk1Identifiant ORCID : https://orcid.org/0000-0002-8836-1577; Rechercher : Chakravarty, Balu1; Rechercher : Liu, Qing Yan1; Rechercher : Iqbal, Umar1Identifiant ORCID : https://orcid.org/0009-0007-8326-0455; Rechercher : Ling, Binbing1Identifiant ORCID : https://orcid.org/0009-0000-6051-9590; Rechercher : Lessard, Etienne1Identifiant ORCID : https://orcid.org/0000-0002-4431-6475; Rechercher : Sheff, Joey1Identifiant ORCID : https://orcid.org/0000-0002-9269-6863; Rechercher : Robotham, Anna1Identifiant ORCID : https://orcid.org/0000-0002-6464-736X; Rechercher : Callaghan, Debbie1; Rechercher : Moreno, Maria1; Rechercher : Comas, Tanya1Identifiant ORCID : https://orcid.org/0009-0001-1862-0043; Rechercher : Ly, Dao1; Rechercher : Stanimirovic, Danica1Identifiant ORCID : https://orcid.org/0000-0001-6678-407X |
|---|
| Affiliation | - Conseil national de recherches du Canada. Thérapeutique en santé humaine
|
|---|
| Format | Texte, Article |
|---|
| Sujet | automated patch-clamp system; epitope; mouse OD1 model; pain; rat Hargreaves model; surface plasmon resonance; VₕH |
|---|
| Résumé | 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. |
|---|
| Date de publication | 2024-08-24 |
|---|
| Maison d’édition | Wiley |
|---|
| Licence | |
|---|
| Dans | |
|---|
| Langue | anglais |
|---|
| Sous presse | Oui |
|---|
| Publications évaluées par des pairs | Oui |
|---|
| Exporter la notice | Exporter en format RIS |
|---|
| Signaler une correction | Signaler une correction (s'ouvre dans un nouvel onglet) |
|---|
| Identificateur de l’enregistrement | 35b1e016-2737-40e4-bcb7-08672dd850ed |
|---|
| Enregistrement créé | 2024-09-10 |
|---|
| Enregistrement modifié | 2024-09-10 |
|---|
