thesis

Quantitative analysis of tumor biomarkers in micro-samples with DNA bases nanodevices

Abstract

The field of DNA nanotechnology aims to create molecular structures and devices by using DNA as an engineering material. The specificity of Watson-Crick base pairing, combined with a dramatic decrease in the cost of synthesis, has made DNA a widely used material for the assembly of molecular structures and dynamic molecular devices for a wide range of applications including smart drug release, cell biology and imaging. The major objective of my PhD work has been to develop novel DNA-based nanodevices for diagnostic applications using non-canonical DNA/DNA interactions (Hoogsteen interactions) that are able to form triplex DNA structures. More specifically, I rationally designed, developed and characterized signal-on electrochemical DNA sensors, based on triplex-forming DNA probes, with improved affinity and specificity of recognition compared to classic electrochemical DNA sensors, based on simple Watson-Crick interactions. Moreover, since such Hoogsteen interactions are strongly pH dependent, I also demonstrated the possibility to control with pH changes DNA strand displacement reaction, an important class of DNA-based reactions, and the self-assembly of DNA nanostructures. The results that I have achieved during my PhD can have implication for the development of DNA nanodevices whose assembly and functionality can be triggered in the presence of specific biological targets, thus offering promising applications in different fields such as diagnosis, synthetic biology, drug release, imaging, smart-nanomaterials and nanoscale component

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