Engineered bacteria detect tumor DNA

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dc.contributor.authorCooper, R.M.
dc.contributor.authorWright, J.A.
dc.contributor.authorNg, J.Q.
dc.contributor.authorGoyne, J.M.
dc.contributor.authorSuzuki, N.
dc.contributor.authorLee, Y.K.
dc.contributor.authorIchinose, M.
dc.contributor.authorRadford, G.
dc.contributor.authorRyan, F.J.
dc.contributor.authorKumar, S.
dc.contributor.authorThomas, E.M.
dc.contributor.authorVrbanac, L.
dc.contributor.authorKnight, R.
dc.contributor.authorWoods, S.L.
dc.contributor.authorWorthley, D.L.
dc.contributor.authorHasty, J.
dc.date.issued2023
dc.description.abstractSynthetic biology has developed sophisticated cellular biosensors to detect and respond to human disease. However, biosensors have not yet been engineered to detect specific extracellular DNA sequences and mutations. Here, we engineered naturally competent <jats:italic>Acinetobacter baylyi</jats:italic> to detect donor DNA from the genomes of colorectal cancer (CRC) cells, organoids, and tumors. We characterized the functionality of the biosensors in vitro with coculture assays and then validated them in vivo with sensor bacteria delivered to mice harboring colorectal tumors. We observed horizontal gene transfer from the tumor to the sensor bacteria in our mouse model of CRC. This cellular assay for targeted, CRISPR-discriminated horizontal gene transfer (CATCH) enables the biodetection of specific cell-free DNA.
dc.description.statementofresponsibilityRobert M. Cooper, Josephine A. Wright, Jia Q. Ng, Jarrad M. Goyne, Nobumi Suzuki, Young K. Lee, Mari Ichinose, Georgette Radford, Feargal J. Ryan, Shalni Kumar, Elaine M. Thomas, Laura Vrbanac, Rob Knight, Susan L. Woods, Daniel L. Worthley, Jeff Hasty
dc.identifier.citationScience, 2023; 381(6658):682-686
dc.identifier.doi10.1126/science.adf3974
dc.identifier.issn0036-8075
dc.identifier.issn1095-9203
dc.identifier.orcidNg, J.Q. [0000-0003-2302-2643]
dc.identifier.orcidSuzuki, N. [0000-0001-9566-8828] [0000-0002-8402-4530]
dc.identifier.orcidRadford, G. [0000-0002-2983-3909]
dc.identifier.orcidThomas, E.M. [0000-0002-9408-8378]
dc.identifier.orcidWoods, S.L. [0000-0002-8955-2017]
dc.identifier.orcidWorthley, D.L. [0000-0003-0374-9124]
dc.identifier.urihttps://hdl.handle.net/2440/142206
dc.language.isoen
dc.publisherAmerican Association for the Advancement of Science (AAAS)
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/2020555
dc.rightsCopyright © 2023 the authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original US government works. https://www.sciencemag.org/about/science-licenses-journal-article-reuse
dc.source.urihttp://dx.doi.org/10.1126/science.adf3974
dc.subjectDNA
dc.subjectbacterium
dc.subjectbacteria
dc.subjectcancer
dc.subjecttumor
dc.subject.meshAnimals
dc.subject.meshHumans
dc.subject.meshMice
dc.subject.meshAcinetobacter
dc.subject.meshColorectal Neoplasms
dc.subject.meshDNA, Neoplasm
dc.subject.meshBiosensing Techniques
dc.subject.meshMutation
dc.subject.meshBioengineering
dc.subject.meshCell-Free Nucleic Acids
dc.titleEngineered bacteria detect tumor DNA
dc.typeJournal article
pubs.publication-statusPublished

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