Peptide Nucleic Acids (PNAs) as Diagnostic Molecules for the Early Detection of Cancer

Eylon Yavin, Medicinal Chemistry, Hebrew University of Jerusalem, Jerusalem, Israel
Ariel D. Levine, Chemistry, Technion, Haifa, Israel
Micael Iv, Chemistry, Technion, Haifa, Israel
Uri Peskin, Chemistry, Technion, Haifa, Israel

PNAs are DNA mimics that consist of a neutral backbone allowing excellent hybridization to complementary DNA and RNA targets.
In my talk I will describe our efforts for designing and using such molecules for cancer diagnostics.

Thiazole orange (TO) has been previously reported by Seitz and co-workers (1) as a surrogate base that when incorporated into a PNA sequence, turns on its fluorescence upon hybridization to a complementary RNA sequence. We have used this approach by designing a PNA molecule that targets the oncogenic form of kRAS (mutated kRAS) and were able to detect this mutation in living cancer cells (2). We have also targeted a long non-coding RNA (lncRNA) that has been found to be highly expressed in colorectal cancer (3). By doing so, we could detect this cancer biomarker in living cells as well as in tissue biopsies from colorectal cancer patients (4). We have now designed and synthesized new red-shifted fluorescent probes that have been successfully incorporated into PNA with the hope that these probes could be used in an in-vivo setting.

References:
1. Kohler, O. et al., ChemBioChem 2005, 6, 69-77.
2. Kam, Y. et al., Mol. Pharm. 2012, 9(3), 685-693.
3. Nissan, A. et al. Int. J. Cancer 2012, 130, 1598-1606.
4. Kam, Y. et al., Cancer Lett. 2014, 352(1), 90-96.