476 Non-viral gene delivery platform for topically treating rare genodermatoses

Gene therapy is the most promising treatment for recessive dystrophic epidermolysis bullosa (RDEB), however genetic cargo delivery efficiency still a technical limitation. Viruses are traditional vector of preference gene therapy, as virus trophism increase tissue specificity. However, drawbacks related with safety and high manufacturing costs have facilitated expansion non-viral vectors, such liposomes cationic polymers. Our group focused on development highly branched polymers to treat RDEB. demonstrated encapsulation full COL7A1 cDNA no toxicity, performing better transfection efficiencies than commercial counterparts in RDEB keratinocytes. In this work, we show research progress expanding polymer technology mRNA ribonucleoprotein complex developing CRISPR/Cas9 based editing therapies edition vivo has been achieved by single topical application, obtaining comparable viral vectors (Ad5). Endosomal escape, peptide decoration being investigated improve avoiding endosomal retention. Storage nanoparticles, formed cargo, at -20C ensures reduction more 6 months. order avoid cold chain challenges, nanoparticles lyophilised, increasing dose concentration facilitating formulation skin absorption enhancers application. Proven ability transfect stem cells combined transfecting multiple plasmids same time, should contribute success prime strategies pursue permanent correction potential >89% all described EB disease-associated mutations. The developed platform shows be adapted wide range approaches RDEB, including novel ones.