The Potential of Gene Therapy for Recessive Dystrophic Epidermolysis Bullosa

K.S. Subramaniam; M.N. Antoniou; J.A. McGrath; S.M. Lwin

Disclosures

The British Journal of Dermatology. 2022;186(4):609-619. 

In This Article

Natural Gene Therapy: Revertant Mosaicism

A naturally occurring phenomenon known as revertant mosaicism has been harnessed as a form of gene therapy in RDEB. This refers to the spontaneous conversion of a mutated somatic cell acquiring a second mutation to self-correct its condition, producing clinically normal patches of skin, as is frequently observed in genetic skin conditions,[42] including RDEB[43] and Kindler EB.[44] Researchers have attempted to generate induced pluripotent stem cells (iPSCs) from clinically normal skin of patients with RDEB to generate naturally gene-corrected RDEB keratinocytes that can be grafted onto wound sites.[45–48] iPSCs can be produced from any somatic cell (e.g. fibroblasts) using reprogramming factors, and can be differentiated into specialized cell types with indefinite expansion, thus resembling embryonic stem cells.[49] Of note, recently, revertant RDEB dermal fibroblasts in addition to keratinocytes from clinically normal patches of skin have also been identified, which may expand future therapeutic options for this monogenic disease.[50]

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