Efficient Dual Cas9 Nickase Correction of a Prevalent Pathogenic LAMB 3 Variant for Junctional Epidermolysis Bullosa.

ABSTRACT: Gene editing facilitated by homology-directed repair represents a promising strategy for precisely correcting pathogenic variants underlying monogenic disorders, including the life-threatening skin blistering condition junctional epidermolysis bullosa (JEB). Frequent reports of unintended off-target genotoxicity associated with conventional Cas9 nuclease editing have increasingly led to the adoption of dual-Cas9 nickases (dual-Cas9n) owing to their improved safety profile. However, rates of precise repair obtained with such strategies remain low. In this study, we establish a dual-Cas9n approach targeting LAMB3, using electroporation to deliver Cas9-nickase ribonucleoproteins and modified single-stranded oligodeoxynucleotide repair templates into primary JEB keratinocytes. Targeting

SUBMITTER: du Rand A 

PROVIDER: S-EPMC11815943 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature