Targeting DNA G4 to investigate ageing biology

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G-quadruplexes are DNA and RNA secondary structures that can form in the human genome and transcriptome. Small-molecules and chemical-biology tools to probe G-quadruplexes structures in cells have been developed over the past decade, but most of this strategies provide a stabilisation of these structure rather than their unfolding. Inducing G-quadruplex unfolding by means of chemical-biology approaches has great potential for therapeutic intervention towards rare genetic diseases like Cockayne Syndrome and ALS, which are both caused by an uncontrolled cellular accumulation of G-quadruplex structures. Souro's project is focused on investigating the application of short chemically-modified antisense oligonucleotides to achieve G-quadruplex destabilisation and unfolding. Although, his main project is focused on the fundamental biophysical understanding of how antisense-targeting approaches can be used to achieve thermodynamic and kinetic destabilisation of G-quadruplex structures, the knowledge generated during this PhD project will be of high relevance to investigate the potential of antisense strategies to treat ALS and Cockayne Syndrome by means of G-quadruplex destabilisation.