{"doi":"10.3389/fbioe.2022.959441","title":"Achieving spatially precise diagnosis and therapy in the mammalian gut using synthetic microbial gene circuits","abstract":"<jats:p>The mammalian gut and its microbiome form a temporally dynamic and spatially heterogeneous environment. The inaccessibility of the gut and the spatially restricted nature of many gut diseases translate into difficulties in diagnosis and therapy for which novel tools are needed. Engineered bacterial whole-cell biosensors and therapeutics have shown early promise at addressing these challenges. Natural and engineered sensing systems can be repurposed in synthetic genetic circuits to detect spatially specific biomarkers during health and disease. Heat, light, and magnetic signals can also activate gene circuit function with externally directed spatial precision. The resulting engineered bacteria can report on conditions <jats:italic>in situ</jats:italic> within the complex gut environment or produce biotherapeutics that specifically target host or microbiome activity. Here, we review the current approaches to engineering spatial precision for <jats:italic>in vivo</jats:italic> bacterial diagnostics and therapeutics using synthetic circuits, and the challenges and opportunities this technology presents.</jats:p>","journal":"Frontiers in Bioengineering and Biotechnology","year":2022,"id":614814,"datarank":0.4335557636844247,"base_score":2.8903717578961645,"endowment":2.8903717578961645,"self_citation_contribution":0.4335557636844247,"citation_network_contribution":0.0,"self_endowment_contribution":0.4335557636844247,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1584382,"name":"Nina E. Short","orcid":null,"position":1,"is_corresponding":false},{"id":1584383,"name":"David T. Riglar","orcid":null,"position":2,"is_corresponding":false},{"id":1584381,"name":"Clare M. Robinson","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Achieving spatially precise diagnosis and therapy in the mammalian gut using synthetic microbial gene circuits","abstract":"<jats:p>The mammalian gut and its microbiome form a temporally dynamic and spatially heterogeneous environment. The inaccessibility of the gut and the spatially restricted nature of many gut diseases translate into difficulties in diagnosis and therapy for which novel tools are needed. Engineered bacterial whole-cell biosensors and therapeutics have shown early promise at addressing these challenges. Natural and engineered sensing systems can be repurposed in synthetic genetic circuits to detect spatially specific biomarkers during health and disease. Heat, light, and magnetic signals can also activate gene circuit function with externally directed spatial precision. The resulting engineered bacteria can report on conditions <jats:italic>in situ</jats:italic> within the complex gut environment or produce biotherapeutics that specifically target host or microbiome activity. Here, we review the current approaches to engineering spatial precision for <jats:italic>in vivo</jats:italic> bacterial diagnostics and therapeutics using synthetic circuits, and the challenges and opportunities this technology presents.</jats:p>","is_dataset_classified":null,"base_score":2.8903717578961645,"endowment":2.8903717578961645,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"36118573","pmcid":"PMC9478464","openalex_id":"https://openalex.org/W4294204426","authors":[],"funders":[{"funder_name":"Wellcome Trust","grant_id":"211230/Z/18/Z","title":null},{"funder_name":"Wellcome Trust","grant_id":"211230","title":"Engineering the microbiome to expose the functional biogeography of the gut"},{"funder_name":"Wellcome Trust","grant_id":"","title":null}],"total_grants":3,"fwci":1.0015,"citation_percentile":0.71179849,"influential_citations":0,"citation_trend":[{"year":2022,"count":1},{"year":2023,"count":2},{"year":2024,"count":4},{"year":2025,"count":7},{"year":2026,"count":3}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.frontiersin.org/articles/10.3389/fbioe.2022.959441/pdf","host_type":"journal"},{"url":"https://www.frontiersin.org/articles/10.3389/fbioe.2022.959441/pdf","host_type":"publisher"},{"url":"https://www.frontiersin.org/articles/10.3389/fbioe.2022.959441/full","host_type":"publisher"},{"url":"https://doi.org/10.3389/fbioe.2022.959441","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/36118573","host_type":"repository"},{"url":"https://doaj.org/article/da935e3d0b2545c7a747d7d1351ef890","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9478464","host_type":"repository"},{"url":"http://hdl.handle.net/10044/1/99350","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC9478464","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC9478464?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.3389/fbioe.2022.959441","host_type":""},{"url":"https://doi.org/https://doi.org/10.3389/fbioe.2022.959441","host_type":""}],"fields_of_study":["Molecular Communication and Nanonetworks","Microfluidic and Bio-sensing Technologies","Single-cell and spatial transcriptomics","0301 basic medicine","03 medical and health sciences"],"mesh_terms":[],"keywords":["Synthetic biology","Microbiome","Gut microbiome","Computational biology","Genetically engineered","Computer science","Function (biology)","Biology","Biochemical engineering","Bioinformatics","Gene","Cell biology","Genetics","Engineering","Bacteria","Biogeography","Gut","Therapy","Microbiota","Diagnostic","Spatial","570","1004 Medical Biotechnology","0699 Other Biological Sciences","610","Bioengineering and Biotechnology","0903 Biomedical Engineering","TP248.13-248.65","Biotechnology"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-02T17:17:10.441912Z","pmid":null,"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":[]}