DynEnON

Gene therapies offer great therapeutic perspectives toward personalized medicine. However, despite considerable efforts, translation of these technologies into clinical applications remains slow and is often hampered by the issue of gene delivery. The intracellular delivery of oligonucleotides is indeed a daunting task due their poor ability to cross biological membranes and their rapid degradation by endogenous nucleases. Viruses are remarkable at performing efficient gene delivery: they ensure chemical stability of the viral gene by its encapsulation within a capsid which actively transports the material to its biological target. Since viral gene delivery can cause severe adverse effects, small molecules able to mimic this process would therefore open new perspectives in gene delivery. The present research project lays out a general methodology to identify synthetic compounds that dynamically encapsulate oligonucleotides and may thus serve as gene carriers. The nanoencapsulation within a synthetic capsid is expected to stabilize oligonucleotides against enzymatic degradation. Furthermore, chemical engineering of the supramolecular carriers will enable active and targeted delivery of unmodified oligonucleotides. The long-term goal of the project is to develop a molecular toolbox for the supramolecular engineering of various oligonucleotides (ssDNA, dsDNA, microRNA, siRNA) with a selective molecular carrier for each application (eg. delivery of antisense DNA to cancer cells) and an extremely straightforward protocol to produce the bioassembly.