Engineered bacteria detect tumor DNA

• 成果类型: Article
• 署名作者: Cooper, Robert M.; Wright, Josephine A.; Ng, Jia Q.; Goyne, Jarrad M.; Suzuki, Nobumi; Lee, Young K.; Ichinose, Mari; Radford, Georgette; Ryan, Feargal J.; Kumar, Shalni; Thomas, Elaine M.; Vrbanac, Laura; Knight, Rob; Woods, Susan L.; Worthley, Daniel L.; Hasty, Jeff
• 署名单位: University of California System; University of California San Diego; University of Adelaide; Flinders University South Australia; University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego; University of California System; University of California San Diego
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-13702
• DOI: 10.1126/science.adf3974
• 发表日期: 2023-08-11
• 页码: 682-686
• 关键词: horizontal gene-transfer; acinetobacter-baylyi; long-term; TRANSFORMATION; diagnostics; generation; organoids; models; cells; vivo

摘要

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.