Modular protein-DNA hybrid nanostructures as a drug delivery platform.

摘要: With the increasing number of identified intracellular drug targets, cytosolic delivery has gained much attention. Despite advances in synthetic carriers, however, construction homogeneous and biocompatible nanostructures a controllable manner still remains challenge translational medicine. Herein, we present modular design assembly functional DNA through sequence-specific interactions between zinc-finger proteins (ZnFs) as platform. Three kinds DNA-binding ZnF domains were genetically fused to various with different biological roles, including targeting moiety, molecular probe, therapeutic cargo. The engineered ZnFs employed distinct modules, incorporated into designed ZnF-binding sequence Y-shaped origami (Y-DNA). resulting Y-DNA (FYDN) showed self-assembled superstructures morphology, strong resistance exonuclease activity multi-modality. We demonstrated general utility our approach by showing efficient PTEN tumour suppressor protein rescue unregulated kinase signaling cancer cells negligible nonspecific cytotoxicity.