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<p>Optogenetic control is used to manipulate the activity of specific cell types in vivo for a variety of biological and clinical applications. Here we report ChReef, an improved variant of the channelrhodopsin ChRmine. ChReef offers minimal photocurrent desensitization, a unitary conductance of 80 fS and closing kinetics of 30 ms, which together enable reliable optogenetic control of cells at low light levels with good temporal fidelity and sustained stimulation. We demonstrate efficient and reliable red-light pacing and depolarization block of ChReef-expressing cardiomyocyte clusters. We used adeno-associated-virus-based gene transfer to express ChReef in retinal ganglion cells, where it restores visual function in blind mice with light sources as weak as an iPad screen. Toward optogenetic hearing restoration, ChReef enables stimulation of the auditory pathway in rodents and non-human primates with nanojoule thresholds, enabling efficient and frequency-specific stimulation by LED-based optical cochlear implants.</p>

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Efficient and sustained optogenetic control of sensory and cardiac systems

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月28日

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  • Alexey Alekseev,
  • Victoria Hunniford,
  • Maria Zerche,
  • Marcus Jeschke,
  • Fadhel El May,
  • Anna Vavakou,
  • Dominique Siegenthaler,
  • Marc A. Hüser,
  • Svenja M. Kiehn,
  • Aida Garrido-Charles,
  • Alexander Meyer,
  • Adrian Rambousky,
  • Theocharis Alvanos,
  • Isabel Witzke,
  • Keila Dara Rojas-Garcia,
  • Martin D. Draband,
  • Lukas Cyganek,
  • Eric Klein,
  • Patrick Ruther,
  • Antoine Huet,
  • Stuart Trenholm,
  • Emilie Macé,
  • Kathrin Kusch,
  • Tobias Bruegmann,
  • Bettina J. Wolf,
  • Thomas Mager,
  • Tobias Moser

摘要

Optogenetic control is used to manipulate the activity of specific cell types in vivo for a variety of biological and clinical applications. Here we report ChReef, an improved variant of the channelrhodopsin ChRmine. ChReef offers minimal photocurrent desensitization, a unitary conductance of 80 fS and closing kinetics of 30 ms, which together enable reliable optogenetic control of cells at low light levels with good temporal fidelity and sustained stimulation. We demonstrate efficient and reliable red-light pacing and depolarization block of ChReef-expressing cardiomyocyte clusters. We used adeno-associated-virus-based gene transfer to express ChReef in retinal ganglion cells, where it restores visual function in blind mice with light sources as weak as an iPad screen. Toward optogenetic hearing restoration, ChReef enables stimulation of the auditory pathway in rodents and non-human primates with nanojoule thresholds, enabling efficient and frequency-specific stimulation by LED-based optical cochlear implants.