299 High efficiency and safe base editor correction of recurrent COL7A1 mutations underlying dominant dystrophic epidermolysis bullosa

Abstract

Dominant dystrophic epidermolysis bullosa (DDEB) is an inherited blistering skin disease caused by heterozygous mutations in COL7A1, which encodes type VII collagen (C7), the major component of anchoring fibrils that maintain the integrity of the dermal-epidermal junction. Most COL7A1 mutations in DDEB are single nucleotide variants, resulting in glycine substitutions within the C7 triple helix. Functionally, such mutations cause impaired assembly or secretion of C7 and result in dominant-negative interference through faulty C7 assembly of wild-type and mutant chains into anchoring fibrils.