Many rare diseases course with affectation of neurosensory organs. Among them, the\nneuroepithelial retina is very vulnerable due to constant light/oxidative stress, but it is also the most\naccessible and amenable to gene manipulation. Currently, gene addition therapies targeting retinal\ntissue (either photoreceptors or the retinal pigment epithelium), as a therapy for inherited retinal\ndystrophies, use adeno-associated virus (AAV)-based approaches. However, efficiency and safety of\ntherapeutic strategies are relevant issues that are not always resolved in virus-based gene delivery and\nalternative methodologies should be explored. Based on our experience, we are currently assessing the\nnovel physical properties at the nanoscale of inorganic gold nanoparticles for delivering genes to the\nretinal pigment epithelium (RPE) as a safe and efficient alternative approach. In this work, we present\nour preliminary results using DNA-wrapped gold nanoparticles (DNA-gold NPs) for successful in vitro\ngene delivery on human retinal pigment epithelium cell cultures, as a proof-of-principle to assess its\nfeasibility for retina in vivo gene delivery. Our results show faster expression of a reporter gene in\ncells transfected with DNA-gold NPs compared to DNA-liposome complexes. Furthermore, we\nshow that the DNA-gold NPs follow different uptake, internalization and intracellular vesicle\ntrafficking routes compared to pristine NPs.
Loading....