Engineering of oligonucleotides for developing first-in-class antibiotics

The crisis of resistant bacteria is occurring worldwide, and this issue has become one of the biggest challenges for the humanity nowadays. Thus, the development of innovative antibiotics is an unmet clinical need.

The main aim of this project is to develop a first-in-class approach for treating the infections caused by the most resistant bacteria in the clinical practice.

This study will provide a targeted strategy for delivering antibiotics at the infection area, with limited toxicity to the patient and less prone to antimicrobial resistance.

Herein, we propose therapeutic oligonucleotides activated by nucleases (TOUCANs) as an alternative for killing multi-drug resistant bacteria.

TOUCANs are a pro-drug system that targets the pathogenic bacteria in a specific manner, followed by the subsequent drug release. Previously, we have demonstrated the use of nucleases as biomarkers for targeting bacteria. Based on this knowledge, we hypothesize that, by incorporating a therapeutic nucleoside analogue (e.g.

Floxuridine) into oligonucleotide probes that specifically target bacteria, we can create a novel drug delivery platform for treating bacterial infections in a safer and more efficient manner.

We believe this work can significantly improve the actual methods for treating bacterial infections worldwide with a simple approach, which I envision to be affordable, fast and reliable.