The origami method for manipulating DNA – first developed in 2006 by Paul Rothemund at Caltech – involves forcing a large viral genome to bend by adding small synthetic DNA sequences to it in solution. The shorter segments attach to the main genome and act as "fasteners" that hold the DNA in a range of shapes such as squares, triangles and stars measuring just 100–150 nm across. Such structures might find their way into a wide range of devices, from ultra-tiny computing components to nanomedical sentries that target and destroy abnormal cells or deliver therapeutics into diseased ones.

Although bare DNA structures (and DNA molecules in general) do not enter cells very easily, a team of researchers led by Mauri Kostiainen of Aalto University has now found that they can be made to transfect cells much more readily by coating them with virus proteins.

The scientists coated DNA origami nanostructures measuring 72 × 92 nm with capsid proteins from a cowpea chlorotic mottle virus (CCMV). This virus is an important model system for chemical virology and can accept various synthetic and protein guest macromolecules inside its capsid. They began by breaking the capsid of the virus into its subunits (the capsid protein) and removed the virus’ RNA. They then let the purified capsid proteins self-assemble on top of the DNA origami surface. The proteins are bound to the DNA nanostructure via electrostatic interactions.

Efficient cell transfection

“Using confocal microscopy imaging, we observe that the origami objects enter human kidney cells much more readily as we increase the amount of added virus proteins,” Kostiainen told “Small amounts of protein produce rolled DNA origami-protein complexes, which enter cells quite efficiently. However, as we continue to add more protein, the DNA structures become completely encapsulated by the capsid, and are able to transfect cells 13 times more efficiently than bare origamis.” Indeed, the efficiency at which the structures target cells also far exceeds that of commercial transfection reagents that we tried as a control, he said.

“In this proof-of-concept experiment, we used plant-virus capsid proteins for coating DNA origamis, but other types of proteins could be envisaged too,” he added. “Adding cell-specific ligands to the proteins, for example, would be a step towards fully targeted drug delivery for cancer treatments.”

The team, which also includes researchers from the University of Helsinki, says that it is now busy combining virus proteins with DNA structures that have distinct shapes and functions. It is also testing different types of virus and coating proteins. “The work described in this story is an excellent starting point for developing diverse biomedical applications for virus-coated DNA nanostructures and there should be plenty of interesting findings ahead,” said Kostiainen.

The research is detailed in Nano Letters.