The recent advancements in synthetic biology have opened up new avenues in medical diagnostics, particularly in cancer detection. A groundbreaking development in this field is the engineering of bacteria to detect specific DNA sequences and mutations associated with tumors. This innovative approach leverages the natural ability of bacteria to take up DNA from their environment, combined with sophisticated genetic engineering, to create living biosensors capable of identifying tumor DNA. The implications of this technology are vast, offering a potential paradigm shift in early cancer detection and monitoring.
Traditional methods of cancer detection, such as imaging and biopsy, often detect cancer at later stages when treatment options are limited. Molecular diagnostics have improved early detection, but these methods can be invasive, expensive, and require complex laboratory infrastructure. The emerging field of synthetic biology offers a promising alternative. By engineering living cells to respond to specific molecular signals, researchers can create biosensors that detect disease markers directly in the body. Engineered bacteria designed to detect cancer represent a significant advancement in the field of biotechnology and medical diagnostics. These genetically modified microorganisms are tailored to recognize specific biomarkers associated with various types of cancer.
In a new study published in the Journal Science led by University of California, San Diego scientists, they engineered bacteria for tumor DNA detection and undertook an innovative approach to cancer diagnostics. They genetically modified naturally competent bacteria, such as Acinetobacter baylyi, enabling them to detect specific DNA sequences associated with tumors. The researchers chose bacteria capable of horizontal gene transfer (HGT), specifically Acinetobacter baylyi. They used CRISPR-Cas systems to modify these bacteria. The CRISPR system was programmed to recognize and integrate specific DNA sequences found in tumor DNA. The focus was on oncogenic mutations, like those in the KRAS gene, which are prevalent in various cancers such as colorectal cancer (CRC).
The authors designed the engineered bacteria to detect specific oncogenic mutations, such as those in the KRAS gene, a common marker in various cancers including colorectal cancer (CRC). These bacteria carry CRISPR-Cas systems programmed to recognize and integrate only the mutated DNA sequences. When these bacteria come into contact with tumor DNA, either in vitro or in a living organism, they incorporate the DNA containing the cancer-specific mutation. This incorporation leads to a change in the bacterial phenotype, such as resistance to a particular antibiotic, which can be easily detected. The bacteria’s ability to detect specific mutations suggests they could identify cancer at a much earlier stage compared to traditional methods. The authors highlighted the possibility of introducing these bacteria into the human body in a non-invasive manner, like oral administration, for continuous monitoring of tumor DNA.
The new biosensing approach offers several advantages over traditional cancer detection methods, first, it can be non-Invasiveness where the bacteria can be introduced into the body non-invasively, through oral administration or rectal enema. Secondly, the bacteria can continuously monitor the gut environment, providing real-time data on the presence of tumor DNA. The new method can potentially detect cancer at a much earlier stage than traditional methods, as it can identify specific DNA mutations associated with early cancer development. Being a living system, these biosensors could be more cost-effective to produce and deploy compared to complex molecular diagnostics. While promising, the clinical application of engineered bacteria as biosensors raises several important considerations: the safety of introducing genetically modified organisms into the human body must be thoroughly evaluated. Moreover, the accuracy of these biosensors in differentiating between benign and malignant cells, and their sensitivity in detecting low levels of tumor DNA, need extensive validation.
Looking ahead, the potential of engineered bacteria in cancer detection is immense. This technology could revolutionize how we diagnose and monitor cancer, making early detection more accessible and less invasive. Additionally, it opens the door for the development of similar biosensors for a wide range of diseases, beyond cancer. The integration of synthetic biology with medical diagnostics promises a new era of precision medicine, where treatments can be tailored and monitored at the molecular level in real time. In conclusion, the use of engineered bacteria as living biosensors for tumor DNA detection represents a significant leap forward in cancer diagnostics. This innovative approach harnesses the power of synthetic biology to offer a more sensitive, non-invasive, and potentially cost-effective method for early cancer detection. As research progresses, these bacteria could become part of personalized medicine approaches, providing early and accurate diagnosis for various types of cancer. They might also be engineered to deliver therapeutic agents directly to tumor sites, acting as a dual diagnostic and therapeutic tool.
Cooper RM, Wright JA, Ng JQ, Goyne JM, Suzuki N, Lee YK, Ichinose M, Radford G, Ryan FJ, Kumar S, Thomas EM, Vrbanac L, Knight R, Woods SL, Worthley DL, Hasty J. Engineered bacteria detect tumor DNA. Science. 2023 ;381(6658):682-686. doi: 10.1126/science.adf3974.Go To Science