Date: 02/09/2021

Qurrat Ul Ain , 1 Estefania V.R. Campos , 1,2 Ariel Huynh,1 Dominik Witzigmann , 3,4 and Sarah Hedtrich 1,5,*

Gene therapies are powerful tools to prevent, treat, and cure human diseases. The application of gene therapies for skin diseases received little attention so far, despite the easy accessibility of skin and the urgent medical need. A major obstacle is the unique barrier properties of human skin, which significantly limits the absorption of biomacromolecules, and thus hampers the efficient delivery of nucleic acid payloads. In this review, we discuss current approaches, successes, and failures of cutaneous gene therapy and provide guidance toward the development of next-generation concepts. We specifically allude to the delivery strategies as the major obstacle that prevents the full potential of gene therapies – not only for skin disorders but also for almost any other human disease.

Do We Need Gene Therapy for Skin Diseases?

Gene therapies, including RNA-based approaches, gene augmentation, and gene editing , are powerful tools to prevent, treat, and cure a multitude of human diseases . The first gene therapy, Glybera, obtained regulatory approval in 2012 and at least eight more followed since then. Modern cutaneous gene therapy was pioneered by Paul Khavari and his group, who published first studies on the delivery of the transglutaminase 1 gene into congenital ichthyosis patient cells using retroviruses back in 1996]. Since then, incredibly fast advancements, especially in the field of CRISPR-based gene editing, have propelled the potential applications of gene therapies. Hence, the drug development pipelines and clinical trials are full of gene therapy-based approaches that provide a new lever for the treatment of previously untreatable conditions  Interestingly, the application of gene therapies for skin-related diseases has received comparably little attention so far, despite the easy accessibility of human skin and the urgent medical need.

Full article: https://www.cell.com/trends/biotechnology/fulltext/S0167-7799(20)30207-9