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DNA analogs (PNAs) as potential molecules for the early detection of cancer

Corresponding author:Dr. Eylon YavinPhD student carrying out work: Yossi KamThe early detection of malignant processes is important for maximizing the medical treatment of cancer when identified early on.With the lack of unequivocal proteinaceous biomarkers of the disease, our group, together with the research groups ofProf. Rubinstein​ and Prof. Nissan, explore the possibility to detect a specific mRNA. We focus our efforts on colon cancer. Several approaches have been proposed for the detection of mRNAs that are up-regulated in cancer cells. One approach is the Molecular Beacon (MB) technology which is based on an oligonucleotide that upon hybridization to a specific mRNA lights up (fluorescent signal). The research which was conducted by the PhD student Yossi Kam explored various MBs for the detection of an important cancer biomarker, namely, the kRAS oncogene. This mRNA has single point mutations allowing us to explore the specificity of the designed MBs. Mr. Kam compared the classical MB (denoted as DNA-MB) to that of PNA (peptide nucleic acid, denoted as PNA-MB). PNA is a DNA analog that has excellent binding affinity to its complementary mRNA and is metabolically much more stable. Both PNA-MB and DNA-MB were designed to light up upon hybridization to wild type kRAS mRNA. Yossi found that in the context of total RNA extracted from different cancer cell lines, the PNA-MB is highly specific to the mRNA and can discriminate the wild type kRAS transcripts at a single base resolution. In comparison, the classical DNA-MB showed no discrimination. Finally, PNA-MB transfected into different cancer cell lines was shown to significantly light up only in cells expressing WT kRAS (PANC-1 cancer cells). This is the first example of a PNA-MB that detects an endogenous mRNA in living cells at a single base resolution.  ​