Gene editing for skin diseases: designer nucleases as tools for gene therapy of skin fragility disorders

• Published in: Experimental physiology Vol. 103; no. 4; pp. 449 - 455
• Main Authors: March, Oliver P., Reichelt, Julia, Koller, Ulrich
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.04.2018
• Subjects: Animals; blistering skin disease; Clustered Regularly Interspaced Short Palindromic Repeats - genetics; CRISPR; CRISPR-Cas Systems - genetics; Epidermolysis bullosa; gene editing; Gene Editing - methods; Gene therapy; Genetic Therapy - methods; Genome editing; Heredity; Humans; Nuclease; Pain; Skin diseases; Skin Diseases - genetics; Skin Diseases - therapy; TALEN; Therapeutic applications; Transcription; Transcription activator-like effector nucleases; Transcription Activator-Like Effector Nucleases - genetics; Wounds; CRISPR; gene therapy; blistering skin disease; epidermolysis bullosa; gene editing; TALEN
• ISSN: 0958-0670; 1469-445X
• DOI: 10.1113/EP086044

New Findings What is the topic of this review? This review concerns current gene editing strategies for blistering skin diseases with respect to individual genetic constellations and distinct conditions. What advances does it highlight? Specificity and safety dominate the discussion of gene editing applications for gene therapy, where a number of tools are implemented. Recent developments in this rapidly progressing field pose further questions regarding which tool is best suited for each particular use. The current treatment of inherited blistering skin diseases, such as epidermolysis bullosa (EB), is largely restricted to wound care and pain management. More effective therapeutic strategies are urgently required, and targeting the genetic basis of these severe diseases is now within reach. Here, we describe current gene editing tools and their potential to correct gene function in monogenetic blistering skin diseases. We present the features of the most frequently used gene editing techniques, transcription activator‐like effector nuclease (TALEN) and clustered regularly interspaced short palindromic repeats/CRISPR‐associated protein 9 (CRISPR/Cas9), determining their preferential application for specific genetic conditions, including the type of mutational inheritance, the targeting site within the gene or the possibility to target the mutation specifically. Both tools have traits beneficial in specific situations. Promising developments in the field engender gene editing as a potentially powerful therapeutic option for future clinical applications.