Encapsulation of RNA with DNA Six-Helix Bundle Nanostructures

A DNA six-helix bundle (6HB) was used as the "RNaseproof" sheath for RNA encapsulation and mimics the helical virus capsid for RNA protection. As a widely used motif in the field of DNA nanotechnology, DNA 6HB contains a cavity with a size of ∼2 nm. Previously, DNA 6HB was used to incorporate a DNA duplex inside of the cavity. Here, RNA that forms the A-form duplex with a diameter slightly larger than 2 nm was successfully incorporated inside the cavity of DNA 6HB via an isothermal process, and the DNA sheath was shown to protect RNA from RNase degradation. The superstructure design of DNA 6HB was then used to encapsulate multiple copies of RNA, suggesting the generality of this strategy. Photocleavable linkers were further used to demonstrate the controlled release of RNA from DNA capsules, which shows the potential of using DNA nanostructures for RNA drug-delivery applications in the future.