Development and evaluation of siRNA-mediated gene silencing strategies for ADO2 therapy utilizing iPSCs model and DMPC-SPIONs delivery system

• First establishment of ADO2-iPSCs from patient urine-derived cells for in vitro disease modeling. • DMPC-SPIONs demonstrated low cytotoxicity and efficient siRNA delivery into ADO2-iPSCs. • siRNA-DMPC-SPIONs achieved 66% reduction of mutant CLCN7 expression without affecting wild-type. • Provides a novel gene silencing strategy for ADO2 and potential for other autosomal dominant diseases.