Synthetic Biology Institute, University of California, San Diego, La Jolla, CA 92093, USA.
Precision Cancer Medicine Theme, South Australia Health and Medical Research Institute, Adelaide, SA 5000, Australia.
Science. 2023 Aug 11;381(6658):682-686. doi: 10.1126/science.adf3974. Epub 2023 Aug 10.
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 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.
合成生物学已经开发出复杂的细胞生物传感器来检测和响应人类疾病。然而，生物传感器尚未被设计用于检测特定的细胞外 DNA 序列和突变。在这里，我们构建了天然感受态的，以检测来自结直肠癌 (CRC) 细胞、类器官和肿瘤基因组的供体 DNA。我们在体外通过共培养实验来表征生物传感器的功能，然后通过将传感器细菌递送到携带结直肠肿瘤的小鼠中来验证其在体内的功能。我们在 CRC 的小鼠模型中观察到了来自肿瘤的水平基因转移到传感器细菌中。这种针对特定 CRISPR 区分的水平基因转移 (CATCH) 的细胞分析方法可实现对特定游离 DNA 的生物检测。
