Engineered bacteria detect tumor DNA

Date

2023

Authors

Cooper, R.M.
Wright, J.A.
Ng, J.Q.
Goyne, J.M.
Suzuki, N.
Lee, Y.K.
Ichinose, M.
Radford, G.
Ryan, F.J.
Kumar, S.

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Journal article

Citation

Science, 2023; 381(6658):682-686

Statement of Responsibility

Robert 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

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Abstract

Synthetic 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.

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Copyright © 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

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