重要的领域是发展一种能够在生物体内检测和识别肿瘤DNA的方法。一种有效的方法是通过工程技术改造细菌,使其具备针对肿瘤特异性序列的识别能力。通过该方法,这些工程菌株能够便捷、高效地检测和报告肿瘤DNA的存在。这项技术的推出在肿瘤研究和临床医学实践中具有广泛的应用价值,有可能成为一种重要的癌症诊断和监测工具。
Engineered bacteria detect tumor DNA.
发表日期:2023 Aug 11
作者:
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
来源:
BIOSENSORS & BIOELECTRONICS
摘要:
合成生物学已经开发出复杂的细胞生物传感器来检测和应对人类疾病。然而,目前尚未成功将生物传感器用于检测特定的细胞外DNA序列和突变。在本研究中,我们设计了天然能力的阿西内特细菌(Acinetobacter baylyi)以检测结直肠癌(CRC)细胞、器官样和肿瘤的供体DNA。我们通过体外共培养实验表征了生物传感器的功能,并在携带结直肠肿瘤的小鼠中进行了体内验证。我们观察到了在我们的CRC小鼠模型中,肿瘤细胞向传感器细菌进行的横向基因转移。这种基于细胞的定向、CRISPR鉴别的横向基因转移(CATCH)细胞实验可实现对特定细胞无料DNA的生物检测。
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.