Lara-Sáez and colleagues developed highly branched poly(β-amino ester)s in this study, which can efficiently deliver CRISPR-Cas9 system into RDEB cells in vitro, to facilitate the deletion of COL7A1 exon 80 containing mutation and restore type VII collagen production, which provides a potential strategy as a topical treatment for RDEB. Here, COL7A1 is linked to recessive dystrophic epidermolysis bullosa.