Genome editing currently represents the most advanced way to precisely correct mutations causing inherited diseases such as genodermatoses. In fact, gene therapy is evolving towards substituting addition approaches by the accurate restoration of gene function through targeted gene modification.  Mutations in COL7A1 resulting in reduced production of type VII collagen, one of the various proteins responsible for epidermal-dermal adhesion, cause recessive dystrophic epidermolysis bullosa (RDEB), a devastating skin fragility disorder. For the last 10 years my laboratory has been addressing the correction of COL7A1 by gene editing using several strategies and nucleases. Recently we have optimized different CRISPR/Cas9-based protocols to make them amenable of clinical translation. In my presentation I will discuss these current gene editing studies involving NHEJ and HDR alternatives under ex vivo and in vivo settings for gene therapy of RDEB and other genodermatoses.