{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Foo GW"],"funding":["Canadian Institutes of Health Research"],"pagination":["3696-3708"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12455656"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["14(9)"],"pubmed_abstract":["Imbalances in the mammalian gut are associated with acute and chronic conditions, and using engineered probiotic strains to deliver synthetic constructs to treat them is a promising strategy. However, high rates of mutational escape and genetic instability <i>in vivo</i> limit the effectiveness of biocontainment circuits needed for safe and effective use. Here, we describe STALEMATE (<b>S</b>equence en<b>TA</b>ng<b>LE</b>d <b>M</b>ulti l<b>A</b>yered gene<b>T</b>ic buff<b>E</b>ring), a dual-layered failsafe biocontainment strategy that entangles genetic sequences to create pseudoessentiality and buffer against mutations. We entangled the colicin E9 immunity protein (Im9) with a thermoregulated meganuclease (TSM) by overlapping the reading frames. Mutations that disrupted this entanglement "],"journal":["ACS synthetic biology"],"pubmed_title":["Genetic Entanglement Enables Ultrastable Biocontainment in the Mammalian Gut."],"pmcid":["PMC12455656"],"funding_grant_id":["PJT 191939"],"pubmed_authors":["Uruthirapathy AS","Heinrichs DE","Zhang CQ","Edgell DR","Foo GW","Batko IZ"],"additional_accession":[]},"is_claimable":false,"name":"Genetic Entanglement Enables Ultrastable Biocontainment in the Mammalian Gut.","description":"Imbalances in the mammalian gut are associated with acute and chronic conditions, and using engineered probiotic strains to deliver synthetic constructs to treat them is a promising strategy. However, high rates of mutational escape and genetic instability <i>in vivo</i> limit the effectiveness of biocontainment circuits needed for safe and effective use. Here, we describe STALEMATE (<b>S</b>equence en<b>TA</b>ng<b>LE</b>d <b>M</b>ulti l<b>A</b>yered gene<b>T</b>ic buff<b>E</b>ring), a dual-layered failsafe biocontainment strategy that entangles genetic sequences to create pseudoessentiality and buffer against mutations. We entangled the colicin E9 immunity protein (Im9) with a thermoregulated meganuclease (TSM) by overlapping the reading frames. Mutations that disrupted this entanglement ","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Sep","modification":"2026-07-15T05:51:43.016Z","creation":"2026-06-30T03:16:03.472Z"},"accession":"S-EPMC12455656","cross_references":{"pubmed":["40914949"],"doi":["10.1021/acssynbio.5c00412"]}}