Phosphorothioated DNA Engineered Liposomes as a General Platform for Stimuli‐Responsive Cell‐Specific Intracellular Delivery and Genome Editing

Abstract

AbstractIntracellular protein delivery is highly desirable for protein drug‐based cell therapy. Established technologies suffer from poor cell‐specific cytosolic protein delivery, which hampers the targeting therapy of specific cell populations. A fusogenic liposome system enables cytosolic delivery, but its ability of cell‐specific and controllable delivery is quite limited. Inspired by the kinetics of viral fusion, we designed a phosphorothioated DNA coatings‐modified fusogenic liposome to mimic the function of viral hemagglutinin. The macromolecular fusion machine docks cargo‐loaded liposomes at the membrane of target cells, triggers membrane fusion upon pH or UV light stimuli, and facilitates cytosolic protein delivery. Our results showed efficient cell‐targeted delivery of proteins of various sizes and charges, indicating the phosphorothioated DNA plug‐in unit on liposomes could be a general strategy for spatial‐temporally controllable protein delivery both in vitro and in vivo.