Novel PNA-based diagnostics for microRNA detection

The PhD project will address the urgent need for improved, low-cost point-of-care
diagnostics in cancer, with particular application in prostate cancer screening and diagnosis.
The goal will be to produce devices suitable for clinical evaluation by the end of the project,
in collaboration with the Department of Surgery and Cancer at Imperial College.

Tumour-derived microRNAs (miRNAs) are emerging as novel biomarkers for the diagnosis
and prognosis of human cancers. We aim to develop an ultrasensitive and minimally
invasive electrochemical technology for the screening of multiple miRNAs in body fluids (e.g.
serum, plasma or urine).

Ladame has demonstrated a novel fluorescence-based sensing strategy for detecting
miRNAs in various biological fluids. It uses a combination of two complementary
hybridization probes based on a synthetic peptide nucleic acid (PNA) scaffold. PNAs show
higher binding affinity, specificity and chemical robustness than DNA or RNA probes making
them attractive for application in diagnostics. Simultaneous binding of both probes leads to
1,4-addition of a nucleophile to electrochemically generated quinoid moieties. This offers the
advantage of direct control of the RNA-templated reaction for improved selectivity. Since
electrochemical methods scale well to extreme miniaturization our strategy holds out the
prospect of multiplexed sensing for several biomarkers.