{"doi":"10.1002/bit.70050","title":"Ultrasound Control of Gene Expression in Human iPSCs via Heat Shock Promoters","abstract":"Inducible systems are crucial tools in biomedical research, offering researchers spatiotemporal control at the cellular level. A promising development in this field is the use of focused ultrasound for controlling gene expression using heat shock promoters (HSPs). Focused ultrasound-induced mild hyperthermia activates the cellular heat shock response, which in turn activates HSPs and subsequently drives gene expression. Here, we utilized a Cre/LoxP system where each HSP drives Cre expression to investigate inducible gene expression with HSPs. Cre-mediated excision at the AAVS1 knock-in cassette results in constitutive expression of GFP. We assessed the performance of six HSPs in human induced pluripotent stem cells (hiPSCs). HSP16F and synHSPB'3 were the most effective, showing 27.7% and 33.5% GFP positivity, respectively, following 1 h of pulsed 42°C incubations. This contrasts with 0.6% and 3.5% GFP positivity at 37°C, indicating 45.9- and 9.7-fold increases, respectively. Increasing the number of HSP-Cre transposons did not significantly affect HSP16F but did enhance synHSPB'3, demonstrating its tunability. We then applied focused ultrasound to elevate the temperature to 42°C, resulting in 18.6% and 45.6% GFP positivity for HSP16F and synHSPB'3, respectively, compared to 0.3% and 6.2% at 37°C. Our design requires only a single, brief heat shock treatment to achieve permanent gene expression, enhancing its safety and feasibility for in vivo applications.","journal":"Biotechnology and Bioengineering","year":2025,"id":546216,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9513,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1438337,"name":"Kama Bell","orcid":null,"position":1,"is_corresponding":false},{"id":1437962,"name":"Hyeonu Heo","orcid":"0000-0003-0116-0471","position":2,"is_corresponding":false},{"id":989054,"name":"Tahir Haideri","orcid":"0000-0003-3566-7537","position":3,"is_corresponding":false},{"id":592038,"name":"Yun Jing","orcid":"0000-0003-1800-0650","position":4,"is_corresponding":false},{"id":270356,"name":"Xiaojun Lian","orcid":"0000-0002-9161-1004","position":5,"is_corresponding":false},{"id":1437961,"name":"Alessandro R. Howells","orcid":"0000-0001-7741-340X","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":null,"created_at":"2026-07-19T02:53:32.285899Z","pmid":"40836509","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}