The 660-nt RNA structure can be transcribed from a DNA template and folds isothermally ( 44). Notably, the simple ssDNA structures ( 41– 43) as well as the 1669-nt scaffold for the octahedron ( 3) can be replicated in vitro ( 3, 41– 43), and these simple single-stranded structures were cloned and replicated in living cells ( 43, 45). In addition, a 1669-nt DNA strand, with the help of five auxiliary strands, was folded into an octahedron structure ( 3). In contrast to the remarkable success of structures self-assembled from multiple components, the progress on designing a single-stranded DNA (ssDNA) or RNA (ssRNA) that can self-fold into a defined shape is limited, and only relatively simple shapes were demonstrated.
Particularly noteworthy are multikilobase, megadalton-scale nanoparticles with arbitrary user-prescribed geometry that are self-assembled from hundreds of synthetic DNA strands, with and without the assistance of a central organizing scaffold strand. Using nucleic acids’ specific base pairing, complex nanostructures have been created with DNA and RNA ( 1– 27), enabling diverse applications ( 28– 40). Biology’s operational principles on the molecular scale motivate synthetic efforts to design replicable, information-bearing polymers that can self-fold into user-prescribed nanoscale shapes. However, a general strategy to construct large single-stranded origami (ssOrigami) remains to be demonstrated where a single-stranded nucleic acid folds into a user-specified shape.įoundational to biological replication, function, and evolution is the transfer of information between sequence-specific polymers (for example, DNA replication, RNA transcription, and protein translation) and the folding of an information-carrying polymer into a compact particle with defined structure and function (for example, protein and RNA folding). The ability to fold de novo designed nucleic acid nanostructures in a similar manner would enable unimolecular folding instead of multistrand assembly and even replication of such structures.
On the other hand, biological macromolecules, such as proteins (or protein domains), typically fold from a single polymer into a well-defined compact structure. In recent years, RNA has also emerged as a unique, programmable material, offering distinct advantages for molecular self-assembly. In particular, multiple DNA strands have been designed to self-assemble into user-specified structures, with or without the help of a long scaffold strand. Over the past three decades, nucleic acids have been used to create a variety of complex nanoscale shapes and devices. Self-folding of an information-carrying polymer into a compact particle with defined structure and function (for example, folding of a polypeptide into a protein) is foundational to biology and offers attractive potential as a synthetic strategy.
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