AUTHORS
Morgan Chevalier, Firas Fadel, Tímea Májer, Dániel Péter Magda, Lili Gerendás, Ferenc Kilin, Zoltán Zsolt Nagy, Arnold Szabó, Botond Roska, Guilherme Testa-Silva
Trends Biotechnol. 2025 Dec;43(12):3236-3252. doi: 10.1016/j.tibtech.2025.07.033. Epub 2025 Aug 29.
ABSTRACT
Engineering infrared light sensitivity in the blind human retina could restore visual function in patients with regional retinal degeneration. However, current approaches are complex and contain non-human biological components. Using rational protein design, we engineered human transient receptor potential vanilloid 1 (hTRPV1) channels (Δ786-840) with temperature sensitivity that shifted from 45 to 41°C, which enabled near-infrared (NIR) light-induced heat activation of mammalian cells at close to physiological temperatures. When expressed in ganglion cells of human retinal explants, Δ786-840 TRPV1 generated robust spiking responses to brief NIR light-induced temperature transients. In addition, increasing intensity of radiation evoked graded responses correlating with increasing firing frequencies. Unlike previous approaches, which used non-human TRPV1 channels, risking immune reactions, and a multicomponent system that poses barriers to clinical implementation, this single-component human-derived approach eliminates immunogenicity concerns, addressing a major challenge to clinical translation, and allows gene delivery using adeno-associated virus (AAV) vectors.
Keywords: TRPV channels; electrophysiology in retinal cells; engineered ion channels; gene therapy; human retina; photothermal stimulation; protein engineering; vision restoration.
Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.
PMID: 40885666 | DOI: 10.1016/j.tibtech.2025.07.033
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