Hybrid RNA/DNA origami nanostructures

Within the past 20 years, structural DNA nanotechnology has evolved from simple DNA tiles composed of a few strands to more advanced DNA origami nanostructures composed of dozens of unique strands. Meanwhile, the shape space of various RNA structures has also significantly expanded, and the tools for creating custom DNA and RNA nanostructures have been developed hand in hand with the ever‑increasing complexity of the designs. Recently, there has been increasing interest in hybrid RNA/DNA origami nanostructures, as the design paradigms created for DNA origami could also be adapted for RNA scaffold folding, thereby paving the way for programmable packaging of gene‑encoding RNA and its delivery, e.g., for the development of vaccines and therapeutics. In this insight, we briefly summarize the evolution of DNA and RNA nanostructures and focus on the recently reported hybrid RNA/DNA origami, their design principles/parameters, properties, and their potential use in gene delivery.

What you will learn

01

Why DNA origami has matured faster than RNA origami, and how hybrid RNA/DNA origami nanostructures (RDONs) aim to combine DNA's structural robustness with RNA's biological versatility

02

How differences between B-form DNA and A-form RNA helices affect RDON design, with 11 bp/turn pitches and asymmetric diagonal crossovers improving folding yield and structural accuracy

03

How mRNA-scaffolded RDONs can be folded, translated into functional protein, and coated or aptamer-modified for gene delivery and vaccine applications

Key interests

Hybrid RNA/DNA origami DNA origami nanostructures RNA nanotechnology mRNA delivery A-form helix design Isothermal folding Gene therapy Vaccine development