Team:CLSB-UK
Project BATMAN
a new way to detect cancer using toehold switches
Late presentation and non-specific symptoms are the main
reasons 1.6 million people worldwide die from lung cancer every year
Dr Sujal Desai, Consultant Chest Radiologist
We have developed a new way to detect cancer at an early stage by measuring micro-RNAs (miRNAs), biomarkers found in blood. We use toehold switches to regulate expression of GFP in response to specific miRNAs. This method could be applied to a myriad of diseases, but we have chosen to use non-small cell lung cancer (NSCLC) as a proof of concept. We hope our work in NSCLC detection demonstrates the potential that toehold switches have to offer as a cheap and effective diagnostic tool.
Late presentation of symptoms is the main reason
why 40,000 people are dying every year from lung cancer
Dr Sujal Desai, Respiratory Consultant
We developed a new way to detect cancer at an early stage by measuring micro-RNAs (miRNA), biomarkers found in blood. We used toehold switches to regulate expression of GFP in response to specific miRNAs. This method could be applied to a myriad of diseases, but we have chosen to use non-small cell lung cancer as a proof of concept.
Biomarkers in the blood
Abnormal levels of miRNAs mir-15b-5p and mir-27b-3p in blood serum are indicative of NSCLC[2]. We have designed two sequence-specific sensors that utilise synthetic riboregulators called toehold switches. These toehold switches detect mir-15b-5p and mir-27b-3p and produce fluorescent reporter proteins in their presence. We designed our sensors to work in a cell-free system, allowing them to be used safely and in a low-tech environment.
Non-small cell lung cancer
Lung cancer is the most common cause of cancer-related mortality, with 1.6 million deaths in 2012. That’s 20% of all reported deaths due to cancer. Non-small cell lung cancer (NSCLC) makes up ~80% of all incidences of lung cancer. 58% of all cases in 2012 were reported in less developed countries.[4] NSCLC is characteristically aggressive and pathologically diverse.[5] Common subtypes include pulmonary adenocarcinoma (~50%) and squamous cell carcinoma (~40%).Treatment still centres around cytotoxic chemotherapy, although new treatments show promise including immunotherapies.[6][3] NSCLC’s high mortality rate is, in large part, down to the late stage at which the disease is normally diagnosed.[7] This often renders surgery, which can curative in early stages, pointless as the tumour has metastasised.[8][9]
About 90% of lung cancers are caused by smoking and as smoking rates have declined, there has been a corresponding reduction in incidence of lung cancers.[10] However, nearly 30% of the global population are still estimated to smoke.[11]
