Part 53 The world, from the past to the present, retold from the timelines.

Part 53

Article: Biotechnology My Blog Title: The world, from the past to the present, retold from the timelines.

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2023: [8.10] Mice-tested engineered bacteria to detect cancer DNA. Despite advances in cancer treatment, colorectal cancer (CRC) remained a significant cause of morbidity and mortality worldwide. Although early cancer detection could improve outcomes, current non-invasive tests, such as faecal immunochemical testing, showed limited accuracy. The fecal immunochemical test (FIT) is used as a screening test for colon cancer. It tests for hidden blood in the stool, which can be an early sign of cancer. FIT only detects human blood from the lower intestines. Medicines and food do not interfere with the test. While effective, invasive diagnostic procedures, such as colonoscopy, are unsuitable for large-scale screening because of their high cost and risk. Colonoscopy is a procedure that requires a certain type of prep and uses a flexible tube to look inside the colon & rectum. In addition, screening programmes using colonoscopy were only available for individuals older than a certain age, usually 45 years. In a recent study, researchers at the University of California San Diego, South Australia Health and Medical Research Institute, and Colonoscopy Clinic used CRISPR to engineer Acinetobacter baylyi, a non-pathogenic bacterium commonly found in soil, to detect specific DNA mutations shed by colorectal cancer (CRC) tumours into the gut lumen. In the intestines, the lumen is the opening inside the bowels. It is surrounded by the other parts of the intestinal wall. The researchers had shown that bacteria take up tumour DNA through natural competence and integrate target sequences into their genome through homologous recombination. Homologous recombination is a type of genetic recombination in which nucleotide sequences are exchanged between two similar or identical molecules of DNA. This prompted a detectable change in the bacteria, allowing sensitive and specific identification of CRC mutations. This proof-of-concept study provided evidence that engineered non-pathogenic bacteria could be used as biosensors to non-invasively detect tumour DNA in the gut, paving the way for the development of novel early cancer detection methods for large-scale CRC screening. In this study, we proved that cell-free DNA released from tumours could be used as an effective signal for bioengineering, providing a new and important input for synthetic biology applications. Our findings confirmed that this approach could be used to diagnose disease within a complex environment such as, but not limited to, the colorectal lumen, said Dr Daniel L. Worthley of Colonoscopy Clinic, who was one of the lead investigators of the study. Although further development is required, this approach could help us detect primary early-stage gastrointestinal tumours. “In the future, depending on the bacterial species used and the mode of administration, its clinical use could be significantly more extensive than that, including metastatic cancers and infections,” he added. Metastatic cancer is cancer that spreads from its site of origin to another part of the body. The study was published in Science. Advances in synthetic biology had enabled reprogramming of microbes into living diagnostics and therapeutics. For example, bacteria could be engineered to detect disease biomarkers and produce easily measurable outputs, such as coloured molecules, in stool or urine. A key advantage of bacterial biosensors was their ability to directly integrate cues from the complex environment of the gut. In the gastrointestinal tract, cell-free DNA has a short half-life because of the activity of intestinal enzymes, such as intestinal deoxyribonuclease (DNase), limiting the ability to analyse faecal samples for tumour DNA. Deoxyribonucleases (DNases) are essential for maintaining genome stability and are involved in processes such as DNA replication, repair and recombination. Engineered bacteria in the gut could capture cell-free DNA released from colorectal cancer CRC tumours before its degradation. Researchers developed a method called ‘Cellular Assay for Targeted, CRISPR-discriminated Horizontal Gene Transfer’, or simply ‘CATCH’, to detect specific extracellular DNA sequences and mutations using bacterial biosensors. In contrast to intracellular DNA (iDNA), which is the DNA located within cell membranes, extracellular DNA (exDNA) represents the DNA located outside thereof; extracellular DNA (exDNA) can be found in any kind of environmental samples including soil, sediments, oceans and freshwater.

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Picture sources: Peakpx.com and Pexels, Pixabay in PowerDirector and other websites:

1:https://www.medillsb.com/images/artistimages/images/342_320610@2x.jpg

2:https://ars.els-cdn.com/content/image/1-s2.0-S1936523321001662-gr7_lrg.jpg

3:https://images.contentstack.io/v3/assets/blt5f400315f9e4f0b3/blt6b5b8a216b095752/681b3d5f0bf88d384dd3cc83/screening_faecal-immunochemical-test_og-image.png?branch=prod

4:https://patient.gastro.org/wp-content/uploads/2021/09/CGH-PatientEd-CRCscreening-2020-768x743.jpg

5:https://journals.sagepub.com/cms/10.1177/15248399221083294/asset/d44c40d4-112b-41e2-b1a0-91b2e9ecbae2/assets/images/large/10.1177_15248399221083294-fig2.jpg

6:https://images.ctfassets.net/yixw23k2v6vo/6d0LCuTvMjUWwO5noZud6E/8a8ad36e6747e09a663ff80aa9893efe/large-fecal-occult-blood-test-types.jpg?fm=webp&fit=thumb&q=65&w=984&h=656

7:https://medium.com/@dheerajbowjani/surgery-for-obscure-lower-gastrointestinal-bleeding-in-india-18d9867fa8cf

8:https://innerbody.imgix.net/blood_supply_intestines.png