474 Ratio-dependent adenine base editing engenders highly efficient correction of RDEB mutations with minimal bystander mutations

Abstract

Recessive dystrophic epidermolysis bullosa (RDEB) is a currently incurable blistering genodermatosis caused by mutations in COL7A1 encoding type VII collagen (C7), the major component of anchoring fibrils. Adenine base editors (ABEs) are a class of gene editor which can install A-T to G-C base pair changes and therefore hold promise for reversing pathogenic COL7A1 variants. Patient-derived fibroblasts harboring c.5047 C>T (p. Arg1683*) in exon 54 of COL7A1 were electroporated with 2ug of mRNA of the ‘ABE8e’ ABE variant and 5ug of single guide (sg)RNA.