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.

The impact of preanalytical variables on the analysis of cell-free DNA from blood and urine samples

“…Further study demonstrated that the analytical performance of the technology is equivalent to that obtained after purification and concentration, with a precision of ∼1% for size features ( Boutonnet et al, 2023 ). In addition, several emerging technologies, including sophisticated cellular biosensors ( Cooper et al, 2023 ), electrochemical biosensors ( Wang et al, 2022 ) and fluorescence-enhancing all-dielectric metasurface biosensors ( Iwanaga et al, 2023 ), can detect the content of cfDNA without complicated processing. These methods with high sensitivity have advantages in low-content detection, but they are not suitable for more detailed analysis of DNA fragments, so they are not generally used for quality control of cfDNA analysis.…”

Addendum and Non-invasive Multiregion, Multisample Tumor Sequencing

“…Bacteria also naturally colonize tumors [13]. That in combination with the uptake of cell-free DNA via a competence mechanism could possibly help enable multiregion, multisample tumor sequencing [14].…”

Addendum and Non-invasive Multiregion, Multisample Tumor Sequencing

“…Bacteria also naturally colonize tumors [11]. That in combination with the uptake of cell-free DNA via a competence mechanism could possibly help enable multiregion, multisample tumor sequencing [12].…”