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, including RDEB and Kindler EB. 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. 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.
The British Journal of Dermatology. 2022;186(4):609-619. © 2022 Blackwell Publishing