Due to their highly specific biological activities and intrinsic biocompatibility, delivery of active proteins into cells represents great interest not only for fundamental research 1 and intracellular sensing, but also for numerous therapeutic applications. However, despite their high potential, proteins suffer from chemical and thermal degradation, kidney clearance, and difficulty to penetrate through biological membranes. In particular, enzymes present a major limitation to be sensitive to both medium and the temperature, leading to the loss of their catalytic activity in inappropriate conditions thus limiting their applicability in both enzyme replacement therapy and enzyme prodrug therapy. Another aspect requiring consideration is the localization of proteins. Indeed, while most therapeutic proteins currently on the market have an extracellular localization, the intracellular transport of active proteins aiming cytosolic targets could strongly expand their exploitation for biomedical purposes. Yet the transport to the cytosol is still a major challenge, mainly due to physical impediment of the cell membrane and possible protein inactivation due to endocytosis. Various vectorization systems have thus been proposed for protein protection and intracellular delivery, such as PEGylation, conjugation with cell-penetrating (CPP) or specifically engineered peptides, and formulations with liposomes or polymeric nanoparticles. DNA represents another promising protein carrier in nanomedicine, due to its intrinsic biocompatibility, programmability and transfectability. In fact, nucleic acids can be readily delivered into cells by using various non-viral cationic transfection agents, among which, cationic lipids represent the most involved vectors in clinical studies. In this view, recently DNA has been bound to β-galactosidase and glucose oxidase in order to both protect and deliver them into the cells by using lipofectamine as transfection agent. In this case individual enzyme molecules were covalently conjugated to several single-stranded DNA oligonucleotides. In another example, three luciferase molecules inside tubular DNA origami nanostructures were delivered into the cells via polyethylenimine transfection vector. A modular protein delivery system was recently proposed by Ryu et al., where 3 different proteins could be bound to 3 extremities of Y-shape DNA nanostructure via DNA-binding zinc-finger protein tags. This system was successfully applied for cytosolic delivery of therapeutic endogenous tumor suppressor PTEN (phosphatase and tension homolog).