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Updated: Jan 30, 2026

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Enhancing prestin oligomerization for superior sonogenetics.

Hsien-Chu Wang1, Thi-Nhan Phan2, Tzu-Han Chen1

  • 1Institute of Molecular Medicine, National Tsing Hua University, Hsinchu 300044, Taiwan.

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|January 29, 2026
PubMed
Summary
This summary is machine-generated.

Improving prestin protein oligomerization enhances sonogenetics for non-invasive neuromodulation. An engineered Prestin variant shows improved efficacy and safety for potential neurological disorder therapies.

Keywords:
Caenorhabditis elegans behaviorneuromodulationprestinsonogeneticsultrasound

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Area of Science:

  • Biotechnology
  • Neuroscience
  • Molecular Engineering

Background:

  • Sonogenetics utilizes ultrasound (US)-responsive proteins for non-invasive cellular control.
  • Prestin, an outer hair cell motor protein, enables US responsiveness for potential therapies in neurodegenerative diseases and epilepsy.
  • Current prestin variants have suboptimal oligomerization, limiting their neuromodulation efficacy.

Purpose of the Study:

  • To enhance prestin's sonogenetic performance by improving its oligomerization.
  • To develop a more effective and safe tool for non-invasive neuromodulation.

Main Methods:

  • Screened bat prestin orthologs and mouse prestin mutants for enhanced US responsiveness.
  • Evaluated prestin variant oligomerization and subcellular localization using live-cell imaging and FRET.
  • Assessed functional responses via calcium imaging in cells and neurons, and *in vivo* neuronal activation in mice using c-Fos staining and behavioral assays.
  • Tested cross-species efficacy in *Caenorhabditis elegans* and confirmed tissue safety histologically.

Main Results:

  • Echolocating bat prestins did not outperform mouse prestin.
  • Engineered Prestin(N548S, V715G) variant showed enhanced oligomerization and membrane localization, leading to stronger calcium influx *in vitro*.
  • *In vivo* studies demonstrated robust neuronal activation and motor function in mice, and significant US-evoked behaviors in *C. elegans*.
  • No adverse histological effects were observed in mouse tissues.

Conclusions:

  • Enhancing prestin oligomerization, not natural echolocating variants, significantly boosts sonogenetic efficacy.
  • Prestin(N548S, V715G) is a potent and biosafe tool for non-invasive neuromodulation.
  • This improved prestin variant shows promise for future therapeutic applications in neurological disorders.