Nucleic Acids and Analogues: Tools for Therapeutic and Biosensoristic Applications

Single-stranded oligonucleotides have been explored in the field of precision medicine both as therapeutics and diagnostic tools. Oligonucleotides that function in a sequence-dependent manner have been used to address diseases that range from neurological to metabolic, as well as to develop vaccines. Until now, their use has been limited by their short half-life in the biological environment. These limiting aspects can now be overcome by resorting to chemical modifications in the drug and using appropriate nanocarriers. Thus, synthetic analogues of oligonucleotides are exploited to increase their application. Peptide nucleic acid (PNA) represents a promising class of synthetic DNA analogues in which the favoured sugar backbone is replaced by N2 aminoethylglycine repeats held together by peptide bonds. In this context, we investigated the relevance of PNAs in therapy and diagnostics. In the first case, we synthesized an antigene anti-Bcl-2 PNA, and we have developed a new delivery system never used before for the transport of PNA based on oncolytic adenoviruses. This promising transport system has already demonstrated its extraordinary effectiveness, as evidenced by the recent development of SARS-CoV vaccines.

Furthermore, we have also used PNAs to support the functionalization of the biosensor development. We covalently bound the PNA to the surface of ZnO nanowires for mRNA CD5 detection, a diagnostic marker of Leukemia. The PNA-based biosensor has also been developed to detect mutations responsible for pathologies such as Brugada syndrome. The wide range of applications denotes the versatility of single-stranded oligonucleotides as a robust therapeutic and diagnostic platform.