Recessive dystrophic epidermolysis bullosa (RDEB) is one of the main types of epidermolysis bullosa, a rare, severe, genetic disease characterized by systemic chronic inflammation, blisters, erosions and extensive chronic wounds on the skin and a tendency to squamous cell carcinoma development. The disease is caused by pathogenic variant of COL7A1 gene encoding the synthesis of type VII collagen (C7), that is the main component of the anchorage fibrils, which maintain the adhesion between the epidermis and the underlying dermis. The disease is debilitating. Treatment methods mainly include supportive measures so the development of treatment methods that directly affect the cause of the disease is very relevant. The article is devoted to the possibility of using one of the most promising treatment strategies of RDEB — gene editing in patients with RDEB by means of specific nucleases, namely TALEN (Transcription activator-like effector nucleases) and CRISPR/Cas (Clustered Regularly Interspaced Short Palindromic Repeats/Crispr-Associated protein) that allows to almost irreversibly restore the C7 synthesis. The method is at preclinical stage. The results of preclinical studies, comparative analysis of used methods, as well as approaches that may help to implement this method of RDEB gene therapy in clinical practice in the nearest future are presented.