Enhanced HDR-mediated correction of heterozygous mutations for recessive dystrophic epidermolysis bullosa.

Gene editing facilitated by homology-directed repair (HDR) holds great potential for treating monogenetic disorders such as recessive dystrophic epidermolysis bullosa (RDEB). However, low efficiency and variability between loci must be overcome for its widespread adoption into personalized therapies. To address these challenges, we developed a highly efficient and versatile gene editing strategy for RDEB that incorporates the small molecule inhibitor M3814 to enhance HDR.

Highly efficient CRISPR/Cas9-mediated exon skipping for recessive dystrophic epidermolysis bullosa.

Gene therapy based on the CRISPR/Cas9 system has emerged as a promising strategy for treating the monogenic fragile skin disorder recessive dystrophic epidermolysis bullosa (RDEB). With this approach problematic wounds could be grafted with gene edited, patient-specific skin equivalents. Precise gene editing using homology-directed repair (HDR) is the ultimate goal, however low efficiencies have hindered progress.