| Download | - View final version: A novel antigen design strategy to isolate single‐domain antibodies that target human Naᵥ1.7 and reduce pain in animal models (PDF, 7.7 MiB)
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| DOI | Resolve DOI: https://doi.org/10.1002/advs.202405432 |
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| Author | Search for: Martina, Marzia1ORCID identifier: https://orcid.org/0009-0008-9732-6483; Search for: Banderali, Umberto1ORCID identifier: https://orcid.org/0000-0003-4034-0782; Search for: Yogi, Alvaro1; Search for: Arbabi Ghahroudi, Mehdi1ORCID identifier: https://orcid.org/0000-0002-8580-6083; Search for: Liu, Hong1; Search for: Sulea, Traian1ORCID identifier: https://orcid.org/0000-0001-5301-8261; Search for: Durocher, Yves1ORCID identifier: https://orcid.org/0000-0002-2268-4111; Search for: Hussack, Greg1ORCID identifier: https://orcid.org/0000-0002-9852-6865; Search for: van Faassen, Henk1ORCID identifier: https://orcid.org/0000-0002-8836-1577; Search for: Chakravarty, Balu1; Search for: Liu, Qing Yan1; Search for: Iqbal, Umar1ORCID identifier: https://orcid.org/0009-0007-8326-0455; Search for: Ling, Binbing1ORCID identifier: https://orcid.org/0009-0000-6051-9590; Search for: Lessard, Etienne1ORCID identifier: https://orcid.org/0000-0002-4431-6475; Search for: Sheff, Joey1ORCID identifier: https://orcid.org/0000-0002-9269-6863; Search for: Robotham, Anna1ORCID identifier: https://orcid.org/0000-0002-6464-736X; Search for: Callaghan, Debbie1; Search for: Moreno, Maria1; Search for: Comas, Tanya1ORCID identifier: https://orcid.org/0009-0001-1862-0043; Search for: Ly, Dao1; Search for: Stanimirovic, Danica1ORCID identifier: https://orcid.org/0000-0001-6678-407X |
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| Affiliation | - National Research Council of Canada. Human Health Therapeutics
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| Format | Text, Article |
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| Subject | automated patch-clamp system; epitope; mouse OD1 model; pain; rat Hargreaves model; surface plasmon resonance; VₕH |
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| 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. |
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| Publication date | 2024-08-24 |
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| Publisher | Wiley |
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| Licence | |
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| In | |
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| Language | English |
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| In press | Yes |
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| Peer reviewed | Yes |
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| Export citation | Export as RIS |
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| Report a correction | Report a correction (opens in a new tab) |
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| Record identifier | 35b1e016-2737-40e4-bcb7-08672dd850ed |
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| Record created | 2024-09-10 |
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| Record modified | 2024-09-10 |
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