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Researchers at Weill Cornell Medicine-Qatar (WCM-Q) participated in a landmark international study in which bacterial cells were reprogrammed to synthesise and deliver potent anti-cancer drugs.
The WCM-Q researchers have worked with scientists at Oxford University and Sheffield University in the UK and Greifswald University in Germany to help build reprogrammable cells from three species of bacteria, Escherichia coli, Pseudomonas putida, and Ralstonia eutropha.
The researchers achieved this by destroying and removing the genetic material from the bacteria cells using a special type of enzyme which causes breaks in both strands of the DNA double helix carried within the chromosomes but leaves the other cellular structures intact and able to function. The resultant ‘SimCells’ (short for simple cells) can be reprogrammed by inserting other genetic material, allowing them to be used for a variety of functions, including the synthesis and delivery of therapeutic drugs. Engineering existing organisms to perform researcher-designed functions in this way is known as synthetic biology and is an extremely promising area of research for the development of new treatments for a wide variety different diseases.
In the study, titled ‘Chromosome-free bacterial cells are safe and programmable platforms for synthetic biology’, the research team used reprogrammed SimCells to synthesize catechol (a potent anticancer drug) from salicylic acid to inhibit lung, brain, and soft-tissue cancer cells in the lab. They also demonstrated that SimCells can be used as a ‘safe agent’ to manufacture and deliver therapeutic drugs because they cannot replicate and do not interfere with the host genome as they do not have chromosomal DNA.
Dr. Frank Schmidt, Proteomics Core Director at WCM-Q, is one of the authors of the paper, which was published in the Proceedings of the United States National Academy of Sciences (PNAS), a high-profile journal.
Dr. Schmidt said the project was led by researchers at the University of Oxford ‘s Department of Engineering Science, in particular Professor Wei E. Huang, Associate Professor of Synthetic Biology, and Graduate Researcher Catherine Fan, while WCM-Q contributed its advanced protein analysis capabilities.
Dr. Schmidt said: “This is a really exciting study because it not only demonstrated that bacteria cells can be manipulated to serve as platforms for delivering drugs that are potentially life-saving, but also that they cannot reproduce themselves and cause dangerous infections or interfere with the DNA of the patient.
“It is wonderful for us at WCM-Q to be able to take part in cutting-edge research projects like this with elite institutions like Oxford, Sheffield and Greifswald and it shows the level of ambition and capability we have here, both at the college and in Qatar in
general.”
The paper states that several species of bacteria are known to associate preferentially with cancer tumors, meaning there is great potential for engineering bacteria to directly sense, target, and deliver anticancer compounds to tumors with a patient’s body. Furthermore, the paper claims that ‘genetic circuits’ (artificial assemblies of genes created in the laboratory) were inserted into the SimCells and found to be able to use the cellular machinery in
them to synthesize proteins and perform important metabolic functions such as the glycolysis pathway, which is essential for cell survival.
WCM-Q’s contribution to the study has been supported by the WCM-Q Biomedical Research Program, a Qatar Foundation-funded program. The full document can be read at https:/www.pnas.org/content/117/12/6752
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29/05/2020
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