Nanoparticles to deliver antisense oligonucleotides aimed at exon skipping therapies

RNA is an important target for therapeutic approach of several diseases and the development of strategies to modulate its function has become the goal of many scientists. Antisense oligonucleotides (AONs) are the most used molecules for RNA targeting. However, the in vivo application of AONs is hampered by their poor cellular uptake through lipophilic cell membranes and their short half-life in biologic fluids due to AONs degradation by serum and intracellular nucleases. Identification of an efficacious and safe delivery system is the main challenge in this area: the use of nanoparticles as vectors for DNA/RNA therapeutic molecules offers a possible solution to these problems. Nanoparticles are easily produced, nonimmunogenic and their subcellular and submicron size allow them to penetrate deeply into tissues through the fine capillaries, crossing the fenestration present in the epithelial lining. In this chapter, we describe the progress that has been made in developing of natural or synthetic delivery systems and the efficacy of nanoparticles-AON complexes used in Duchenne exon skipping therapy.