DNA origami structures can be programmed into arbitrary shapes with nanometer scale precision, which opens up numerous attractive opportunities to engineer novel functional materials. One intriguing possibility is to use DNA origamis for fully tunable, targeted, and triggered drug delivery. In this work, we demonstrate the coating of DNA origami nanostructures with virus capsid proteins for enhancing cellular delivery. Our approach utilizes purified cowpea chlorotic mottle virus capsid proteins that can bind and self-assemble on the origami surface through electrostatic interactions and further pack the origami nanostructures inside the viral capsid. Confocal microscopy imaging and transfection studies with a human HEK293 cell line indicate that protein coating improves cellular attachment and delivery of origamis into the cells by 13-fold compared to bare DNA origamis. The presented method could readily find applications not only in sophisticated drug delivery applications but also in organizing intracellular reactions by origami-based templates.

DNA origami structures have great potential as functional platforms in various biomedical applications. Many applications, however, are incompatible with the high Mg concentrations commonly believed to be a prerequisite for maintaining DNA origami integrity. Herein, we investigate DNA origami stability in low-Mg buffers. DNA origami stability is found to crucially depend on the availability of residual Mg ions for screening electrostatic repulsion. The presence of EDTA and phosphate ions may thus facilitate DNA origami denaturation by displacing Mg ions from the DNA backbone and reducing the strength of the Mg -DNA interaction, respectively. Most remarkably, these buffer dependencies are affected by DNA origami superstructure. However, by rationally selecting buffer components and considering superstructure-dependent effects, the structural integrity of a given DNA origami nanostructure can be maintained in conventional buffers even at Mg concentrations in the low-micromolar range.

DNA nanotechnology holds substantial promise for future biomedical engineering and the development of novel therapies and diagnostic assays. The subnanometer‐level addressability of DNA nanostructures allows for their precise and tailored modification with numerous chemical and biological entities, which makes them fit to serve as accurate diagnostic tools and multifunctional carriers for targeted drug delivery. The absolute control over shape, size, and function enables the fabrication of tailored and dynamic devices, such as DNA nanorobots that can execute programmed tasks and react to various external stimuli. Even though several studies have demonstrated the successful operation of various biomedical DNA nanostructures both in vitro and in vivo, major obstacles remain on the path to real‐world applications of DNA‐based nanomedicine. Here, we summarize the current status of the field and the main implementations of biomedical DNA nanostructures. In particular, we focus on open challenges and untackled issues and discuss possible solutions.

In this communication, we present a nanoscale reactor assembled from tuneable and spatially addressable tubular DNA origami units. We can controllably combine separate origami units equipped with glucose oxidase (GOx) and horseradish peroxidase (HRP), and demonstrate efficient GOx/HRP enzyme cascade reaction inside the tube. The reactor could be utilized as a nanoscale diagnostic tool, and modularity of the proposed system would further enable more complex reactions.