| Title: |
A novel antigen design strategy to isolate single‐domain antibodies that target human Naᵥ1.7 and reduce pain in animal models |
| Authors: |
Martina, Marzia; Banderali, Umberto; Yogi, Alvaro; Arbabi Ghahroudi, Mehdi; Liu, Hong; Sulea, Traian; Durocher, Yves; Hussack, Greg; van Faassen, Henk; Chakravarty, Balu; Liu, Qing Yan; Iqbal, Umar; Ling, Binbing; Lessard, Etienne; Sheff, Joey; Robotham, Anna; Callaghan, Debbie; Moreno, Maria; Comas, Tanya; Ly, Dao; Stanimirovic, Danica |
| Publisher Information: |
Wiley |
| Publication Year: |
2024 |
| Collection: |
National Research Council Canada: NRC Publications Archive |
| Subject Terms: |
automated patch-clamp system; epitope; mouse OD1 model; pain; rat Hargreaves model; surface plasmon resonance; VₕH |
| Description: |
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. ; Peer reviewed: Yes ; NRC publication: Yes |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| ISSN: |
2198-3844 |
| Relation: |
Advanced Science, Publication date: 2024-08-24 |
| DOI: |
10.1002/advs.202405432 |
| Availability: |
https://doi.org/10.1002/advs.202405432; https://nrc-publications.canada.ca/eng/view/ft/?id=35b1e016-2737-40e4-bcb7-08672dd850ed; https://nrc-publications.canada.ca/eng/view/object/?id=35b1e016-2737-40e4-bcb7-08672dd850ed; https://nrc-publications.canada.ca/fra/voir/objet/?id=35b1e016-2737-40e4-bcb7-08672dd850ed |
| Rights: |
Creative Commons Attribution 4.0 International (CC BY 4.0) (https://creativecommons.org/licenses/by/4.0/) ; Creative Commons Attribution 4.0 International (CC BY 4.0) (https://creativecommons.org/licenses/by/4.0/deed.fr) |
| Accession Number: |
edsbas.E3DD1BB4 |
| Database: |
BASE |