Researchers at Weill Cornell Medicine-Qatar (WCM-Q) have taken part in a landmark international study in which bacteria cells were reprogrammed to synthesize and deliver a potent anti-cancer drug.
The WCM-Q researchers worked with scientists at the University of Oxford and the University of Sheffield in the UK and the University of Greifswald in Germany to help construct reprogrammable cells from three species of bacteria – Escherichia coli, Pseudomonas putida and Ralstonia eutropha.
The researchers ‘destroyed’ and removed 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’ (or 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 of 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 anti-cancer 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, Director of the Proteomics Core at WCM-Q, is one of the authors of the paper, which was published in the Proceedings of the National Academy of Sciences of the United States of America (PNAS). The project was led by researchers at the Department of Engineering Science at the University of Oxford.
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.
He said that it’s wonderful to be able to take part in cutting-edge research projects like this with elite institutions like Oxford, Sheffield and Greifswald. It shows the level of ambition and capability at WCM-Q and in Qatar in general.
According to the paper, several species of bacteria ‘preferentially’ associate with cancer tumors, providing great potential for researchers to engineer bacteria to sense, target and deliver anti-cancer compounds directly to tumors within the patient’s body.
Additionally, the paper asserts that ‘genetic circuits’ (artificial assemblies of genes created in the lab) inserted into SimCells and were found to be able to utilise the cellular machinery to synthesize proteins and carry out important metabolic functions such as the glycolysis pathway, which is essential for cell survival. Some SimCells generated by the researchers were able to survive for as long as 10 days.
The study was supported by the Biomedical Research Program at WCM-Q, a programme funded by Qatar Foundation. The paper can be read in full through this link.