In vivo spatiotemporal control of voltage-gated ion channels by using photoactivatable peptidic toxins

New publication in Nature Communication:

Smartox is specialized in disulfide-rich peptides engineering and recently published with collaborators new results. In this publication, several complex peptides with ion channel modulation properties have been conjugated to a UV-cleavable protecting group. UV-irradiation at a specific localization lead to peptide activation and local ion channel modulation.

Photoactivatable drugs targeting ligand-gated ion channels open up new opportunities for light-guided therapeutic interventions. Photoactivable toxins targeting ion channels have the potential to control excitable cell activities with low invasiveness and high spatiotemporal precision. As proof-of-concept, we develop HwTxIV-Nvoc, a UV light-cleavable and photoactivatable peptide that targets voltage-gated sodium (NaV) channels and validate its activity in vitro in HEK293 cells, ex vivo in brain slices and in vivo on mice neuromuscular junctions. We find that HwTxIV-Nvoc enables precise spatiotemporal control of neuronal NaV channel function under all conditions tested. By creating multiple photoactivatable toxins, we demonstrate the broad applicability of this toxin-photoactivation technology.

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