Engineered bacteria detect tumor DNA

Author:

Cooper Robert M.1ORCID,Wright Josephine A.2ORCID,Ng Jia Q.3ORCID,Goyne Jarrad M.2,Suzuki Nobumi23ORCID,Lee Young K.3ORCID,Ichinose Mari23ORCID,Radford Georgette3ORCID,Ryan Feargal J.24ORCID,Kumar Shalni5,Thomas Elaine M.3ORCID,Vrbanac Laura3ORCID,Knight Rob6789ORCID,Woods Susan L.23ORCID,Worthley Daniel L.210ORCID,Hasty Jeff1569ORCID

Affiliation:

1. Synthetic Biology Institute, University of California, San Diego, La Jolla, CA 92093, USA.

2. Precision Cancer Medicine Theme, South Australia Health and Medical Research Institute, Adelaide, SA 5000, Australia.

3. Adelaide Medical School, University of Adelaide, Adelaide, SA 5000, Australia.

4. Flinders Health and Medical Research Institute, Flinders University, Bedford Park, SA 5042, Australia.

5. Department of Bioengineering, University of California, San Diego, La Jolla, CA 92093, USA.

6. Molecular Biology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.

7. Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA.

8. Department of Computer Science and Engineering, University of California, San Diego, La Jolla, CA 92093, USA.

9. Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA 92093, USA.

10. Colonoscopy Clinic, Brisbane, QLD 4000, Australia.

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 Acinetobacter baylyi 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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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