Enhanced HDR-mediated correction of heterozygous COL7A1 mutations for recessive dystrophic epidermolysis bullosa.

ABSTRACT: 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. We focused on three RDEB causative COL7A1 mutations not previously targeted by existing gene therapies. Editing was achieved using Cas9-nuclease ribonucleoproteins with short single-stranded DNA donor templates, and outcomes were assessed with an Oxford Nanopore Technology sequencing analysis pipeline. We demonstra

SUBMITTER: Hunt JMT 

PROVIDER: S-EPMC11872078 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature