HyPlex · Hybrid polymer nanoparticles as gene vectors

Gene therapy has long been seen as a promising solution to unmet clinical needs and the licencing of gene therapy SARS-CoV-2 vaccines has provided a flavour of the technology’s potential. However, gene therapy still faces significant challenges in clinical and commercial translation including the need for effective and safe delivery vectors. Polymeric nanoparticles offer great flexibility in gene vectors design, improved stability and easier scale-up of production compared to lipid nanoparticles but often suffer from cytotoxicity and underperformance in vivo. The goal of HyPlex is to develop the next generation polymeric nanovectors which can easily be functionalised to further improve delivery efficacy. The project will develop novel chemistry to achieve polylysine/polyacrylate hybrid nanogels. Functionalisation of nanogels will be demonstrated by the introduction of mannose, a common cell binding motive as well as diethylene glycol ethyl ether arylate to optimise the hydrophilic/hydrophobic balance. In an interdisciplinary approach gene loading and cell transfection will be studied up to in vitro level. The project results will be exploited as part of an ongoing commercialisation initiative at RCSI, which will provide the applicant with a unique experience in research translation and commercialisation. The high-level science is complemented by bespoke training activities, which will significantly advance the career opportunities of the applicant. Project results will be communicated to peers as well as the public with specific focus on encouraging female secondary school pupils to take up scientific careers.