Single stem cell gene therapy for genetic skin disease

Abstract

Stem cell gene therapy followed by transplantation into damaged regions of the skin has been successfully used to treat genetic skin blistering disorder. Usually, many stem cells are virally transduced to obtain a sufficient number of genetically corrected cells required for successful transplantation, as genetic insertion in every stem cell cannot be precisely defined. In this issue of EMBO Molecular Medicine, Droz-Georget Lathion et al developed a new strategy for ex vivo single cell gene therapy that allows extensive genomic and functional characterization of the genetically repaired individual cells before they can be used in clinical settings.

Figure 1. Strategy developed for safe ex vivo gene therapy

Keratinocyte stem cells from RDEB patient are isolated and infected ex vivo with viruses carrying COL7A1 cDNA to correct their function, and colonies arising from a single transduced cell are cloned, selected for their ability to produce collagen 7, and expanded in vitro. Their safety is then evaluated by assessing their genomic integrity and oncogenic potential. The clones that expressed Col VII and did not present safety issues are stimulated to reconstruct the epidermis that will be grafted onto the recipient.