RNA Aptamer development for epigenetic control in neuropathic pain with specific delivery system: from theoretical to in vivo studies

The project aims to develop novel RNA aptamers against the DNMT3a to control neuropathic pain. RNA aptamers are single stranded molecules showing very high affinity and selectivity towards diverse targets. Because RNA extreme flexibility hampers the experimental characterization important outcomes are continuously derived by in silico investigations. We aim to develop RNA aptamers to target DNMT3a with a combined approach of experimental and theoretical methods. DNMTs are responsible for the fundamental epigenetic mechanisms regulating gene expression and are of great interest as targeting systems for several diseases. Abnormality of DNMT3a action is demonstrated to be correlated to neuropathic pain (NP). We use theoretical methods, such as molecular modelling and simulations, docking and deep learning algorithms to design or derive RNA candidates, whose efficacy in inhibiting DNMT3a in neuronal cells will be validated and optimized with experimental in vitro and in vivo assays. NMR studies will confirm the structural results of modelling and simulations. A proper delivery system will be created to allow the achievement of the neuronal cell to target DNMT3a. Finally, cellular lines and animal models investigations will confirm the inhibition of methylase activity and the efficacy of selected aptamer candidates to control epigenetic mechanism in the NP.