{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE311nnn/GSE311869/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE311869"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Truncated Gpr114-based ultrasound-hypersensitive gene circuit for controlled expression of therapeutics","description":"Sonogenetics possesses significant potential for modulating cellular functions and behaviors. However, developing hypersensitive ultrasound (US)-responsive receptors presents a substantial challenge. Here, we utilized AlphaFold3 and molecular dynamics simulation technology to identify a hypersensitive Gpr114 protein variant (T-Gpr114) that can be activated by short-pulse US stimulation. We then engineered sonogentic macrophages (MΦ) using T-Gpr114 and integrated with an engineered genetic circuit, enabling high-performance expression of the nuclear factor ID3 upon short-pulse US stimulation. In mice, sonogentic-MΦ suppressed tumor growth without causing obvious toxicity and outperformed their constitutively expressing counterparts. Single-cell RNA sequencing revealed that engineered sonogentic-MΦ exhibit enhanced phagocytosis and improved recruitment of CD8+ T cells compared to cells with constitutive ID3 expression. This T-Gpr114-based US-hypersensitive gene circuit can be extended to remotely control the activation of various cell types, thereby facilitating the programming of therapeutic cells and enhancing their suitability for clinical translation.","dates":{"publication":"2026/07/03"},"accession":"GSE311869","cross_references":{"GSM":["GSM9333703","GSM9333705","GSM9333704"],"GPL":["34290"],"GSE":["311869"],"taxon":["Mus musculus"]}}