Context-Dependent Strategies for Enhanced Genome Editing of Genodermatoses

• Published in: Cells (Basel, Switzerland) Vol. 9; no. 1; p. 112
• Main Authors: March, Oliver Patrick, Kocher, Thomas, Koller, Ulrich
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 02.01.2020; MDPI
• Subjects: Cell cycle; designer nucleases; Disease; DNA repair; dna repair pathways; Double-strand break repair; Epidermolysis bullosa; Exons - genetics; Gene Editing; Genes; Genetic Therapy; genodermatoses; genome editing; Genomes; Homologous Recombination - genetics; Humans; keratinopathies; Mutation; Nucleotide sequence; Phenotypes; Review; Skin; Skin - pathology; Skin diseases; Skin Diseases - genetics; Skin Diseases - therapy; Structural proteins; genome editing; epidermolysis bullosa; designer nucleases; genodermatoses; DNA repair pathways; keratinopathies
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells9010112

The skin provides direct protection to the human body from assault by the harsh external environment. The crucial function of this organ is significantly disrupted in genodermatoses patients. Genodermatoses comprise a heterogeneous group of largely monogenetic skin disorders, typically involving mutations in genes encoding structural proteins. Therapeutic options for this debilitating group of diseases, including epidermolysis bullosa, primarily consist of wound management. Genome editing approaches co-opt double-strand break repair pathways to introduce desired sequence alterations at specific loci. Rapid advances in genome editing technologies have the potential to propel novel genetic therapies into the clinic. However, the associated phenotypes of many mutations may be treated via several genome editing strategies. Therefore, for potential clinical applications, implementation of efficient approaches based upon mutation, gene and disease context is necessary. Here, we describe current genome editing approaches for the treatment of genodermatoses, along with a discussion of the optimal strategy for each genetic context, in order to achieve enhanced genome editing approaches.