ArticleNature communications2026
Truncated Gpr114-based ultrasound-hypersensitive gene circuit for controlled expression of therapeutics.
Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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12 authors.
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Abstract
Sonogenetic holds great potential for modulating cellular functions and behaviors. However, developing hypersensitive ultrasound (US)-responsive receptors remains a substantial challenge. Here, we combine AlphaFold3 prediction with molecular dynamics simulations to identify a hypersensitive Gpr114 protein variant (T-Gpr114) that responds to short-pulse US stimulation for activation. We further design sonogenetic macrophages (MΦ) by fusing T-Gpr114 to a synthetic genetic circuit, this circuit initiates expression of the transcription factor ID3 upon short-pulse US treatment. In vivo assays using female tumor-bearing mice demonstrate that sonogenetic-MΦ suppress tumor growth with no obvious systemic toxicity, and exhibit enhanced anti-tumor efficacy relative to cells with constitutive ID3 expression. Single-cell RNA sequencing reveals that sonogentic-MΦ potentiate the recruitment recruitment of CD8
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