{"doi":"10.1093/nar/gkaf1290","title":"Metabolite-responsive scaffold RNAs for dynamic CRISPR transcriptional regulation","abstract":"CRISPR activation is a powerful tool to upregulate a vast array of genes in many different contexts. However, there are few dynamic CRISPR transcriptional programs, which limit its usage in the creation of living biosensors, self-regulating microbial factories, or conditional therapeutics. Here, we address this limitation by embedding a molecular switch directly into a guide RNA to create a combined sensor-actuator called a metabolite-responsive scaffold RNA (MR-scRNA). We demonstrate the regulatory potential for MR-scRNAs by conditionally activating genes in three different kingdoms of life. We create MR-scRNAs responsive to two distinct metabolites, theophylline and tryptophan, by swapping the molecular switch used. MR-scRNAs respond quickly in a dose-dependent manner specifically to their target metabolite and enhance biochemical production when used as a dynamic regulator of pathway enzyme expression. The broad functionality and ease of design of the MR-scRNAs offer a promising tool for dynamic cellular regulation.","journal":"Nucleic Acids Research","year":2025,"id":535507,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9554,"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":662266,"name":"Helena Hansen","orcid":"0000-0003-0569-1392","position":1,"is_corresponding":false},{"id":235164,"name":"Blake A. Richards","orcid":"0000-0001-9662-2151","position":2,"is_corresponding":false},{"id":1419585,"name":"Hayeon Park","orcid":null,"position":3,"is_corresponding":false},{"id":1419586,"name":"Antonio G Goncalves","orcid":null,"position":4,"is_corresponding":false},{"id":1046280,"name":"Ayushi Agrawal","orcid":"0000-0001-7081-3304","position":5,"is_corresponding":false},{"id":486673,"name":"Mark Blenner","orcid":"0000-0001-9274-3749","position":6,"is_corresponding":false},{"id":933649,"name":"Wilfred Chen","orcid":"0000-0002-6386-6958","position":7,"is_corresponding":false},{"id":1052258,"name":"Anthony M Stohr","orcid":"0000-0002-2388-1723","position":0,"is_corresponding":true}],"reference_count":76,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:51:56.297114Z","pmid":"41277686","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":[]}