Researchers at Massachusetts General Hospital engineered a bespoke CRISPR-Cas9 base editor targeting the ACTA2 gene mutation underlying multisystemic smooth muscle dysfunction syndrome (MSMDS), a fatal pediatric vascular disorder. In mouse models, the precise gene correction improved survival and reduced disease phenotypes in the vasculature and brain. This personalized gene editing approach overcomes limitations of conventional Cas9 therapy and underscores the potential for CRISPR-based treatments in rare, lethal genetic diseases with no effective current cures.