Genetic Engineering Publications - GEG Tech top picks

Type XVII collagen is crucial for maintaining stability between the different layers of the skin, between the dermis and the epidermis. Mutations in COL17A1, the gene encoding collagen XVII, have been implicated in a debilitating inherited form of epidermolysis bullosa (EB). Although genetic correction using CRISPR-Cas9 has emerged as a promising strategy to treat genetic diseases, there is no method to treat EB by restoring COL17A1 function. In a recent study, researchers developed a patient-specific proximal matched nicking method to reframe a homozygous 2-bp deletion in exon 52 of COL17A1, a mutation commonly seen in patients with junctional EB (JEB). Paired Notch-based COL17A1 editing led to COL17A1 reframing in primary JEB keratinocytes and three-dimensional (3D) skin models, restoring collagen XVII localization and function. The results show for the first time that COL17A1 gene reframing via paired Cas9 nickases is a highly effective and safe option for the treatment of JEB and potentially other genetic defects caused by pathogenic frameshift mutations. The results also demonstrate the superiority of Cas9-nickase-based targeting over wild-type Cas9-based strategies for gene reframing, which can be adapted to other diseases beyond EB.