Engineered bacteria detect tumor DNA

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

doi:10.1126/science.adf3974

Engineered bacteria detect tumor DNA

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

Research output: Contribution to journal › Article › peer-review

38 Citations (Scopus)

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.

Original language	English
Pages (from-to)	682-686
Number of pages	5
Journal	Science (New York, N.Y.)
Volume	381
Issue number	6658
DOIs	https://doi.org/10.1126/science.adf3974
Publication status	Published - 10 Aug 2023

Keywords

synthetic biology
cellular biosensors
cancer detection

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1126/science.adf3974Licence: In Copyright

Cite this

@article{48a128b5300b46bbaddc04f8b58dcf13,

title = "Engineered bacteria detect tumor DNA",

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.",

keywords = "synthetic biology, cellular biosensors, cancer detection",

author = "Cooper, {Robert M.} and Wright, {Josephine A.} and Ng, {Jia Q.} and Goyne, {Jarrad M.} and Nobumi Suzuki and Lee, {Young K.} and Mari Ichinose and Georgette Radford and Ryan, {Feargal J.} and Shalni Kumar and Thomas, {Elaine M.} and Laura Vrbanac and Rob Knight and Woods, {Susan L.} and Worthley, {Daniel L.} and Jeff Hasty",

year = "2023",

month = aug,

day = "10",

doi = "10.1126/science.adf3974",

language = "English",

volume = "381",

pages = "682--686",

journal = "Science (New York, N.Y.)",

issn = "1095-9203",

publisher = "PubMed",

number = "6658",

}

TY - JOUR

T1 - Engineered bacteria detect tumor DNA

AU - Cooper, Robert M.

AU - Wright, Josephine A.

AU - Ng, Jia Q.

AU - Goyne, Jarrad M.

AU - Suzuki, Nobumi

AU - Lee, Young K.

AU - Ichinose, Mari

AU - Radford, Georgette

AU - Ryan, Feargal J.

AU - Kumar, Shalni

AU - Thomas, Elaine M.

AU - Vrbanac, Laura

AU - Knight, Rob

AU - Woods, Susan L.

AU - Worthley, Daniel L.

AU - Hasty, Jeff

PY - 2023/8/10

Y1 - 2023/8/10

N2 - 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.

AB - 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.

KW - synthetic biology

KW - cellular biosensors

KW - cancer detection

UR - http://www.scopus.com/inward/record.url?scp=85167680928&partnerID=8YFLogxK

UR - http://purl.org/au-research/grants/NHMRC/2020555

U2 - 10.1126/science.adf3974

DO - 10.1126/science.adf3974

M3 - Article

C2 - 37561843

AN - SCOPUS:85167680928

SN - 1095-9203

VL - 381

SP - 682

EP - 686

JO - Science (New York, N.Y.)

JF - Science (New York, N.Y.)

IS - 6658

ER -

Engineered bacteria detect tumor DNA

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this