RNA Self-Assembly and RNA Nanotechnology

Abstract

CONSPECTUS: Nanotechnology's central goal involves the direct control of matter at the molecular nanometer scale to build nanofactories, nanomachines, and other devices for potential applications including electronics, alternative fuels, and medicine. In this regard, the nascent use of nucleic acids as a material to coordinate the precise arrangements of specific molecules marked an important milestone in the relatively recent history of nanotechnology. While DNA served as the pioneer building material in nucleic acid nanotechnology, RNA continues to emerge as viable alternative material with its own distinct advantages for nanoconstruction. Several complementary assembly strategies have been used to build a diverse set of RNA nanostructures having unique structural attributes and the ability to self-assemble in a highly programmable and controlled manner. Of the different strategies, the architectonics approach uniquely endeavors to understand integrated structural RNA architectures through the arrangement of their characteristic structural building blocks. Viewed through this lens, it becomes apparent that nature routinely uses thermodynamically stable, recurrent modular motifs from natural RNA molecules to generate unique and more complex programmable structures. With the design principles found in natural structures, a number of synthetic RNAs have been constructed. The synthetic nanostructures constructed to date have provided, in addition to affording essential insights into RNA design, important platforms to characterize and validate the structural self-folding and assembly properties of RNA modules or building blocks. Furthermore, RNA nanoparticles have shown great promise for applications in nanomedicine and RNA-based therapeutics. Nevertheless, the synthetic RNA architectures achieved thus far consist largely of static, rigid particles that are still far from matching the structural and functional complexity of natural responsive structural elements such as the ribosome, large ribozymes, and riboswitches. Thus, the next step in synthetic RNA design will involve new ways to implement these same types of dynamic and responsive architectures into nanostructures functioning as real nanomachines in and outside the cell. RNA nanotechnology will likely garner broader utility and influence with a greater focus on the interplay between thermodynamic and kinetic influences on RNA self-assembly and using natural RNAs as guiding principles.

De novo design of an RNA tile that self-assembles into a homo-octameric nanoprism

“…Here we expand the design principle to achieve higher structural complexity along this direction. Besides addressing the fundamental challenge in programmed RNA self-assembly, we believe that such a study will increase our capability of rationally designing RNA nanostructures 33,34 to meet the needs of potential applications such as siRNA delivery 5,6 and construction of in vivo RNA machineries 4 . In addition, we have observed a surprising but interesting phenomenon.…”

Bubbled RNA‐Based Cargo for Boosting RNA Interference

“…In addition to its range of inherent biological activities, molecular simplicity, and ease of modification have also accelerated the progress of RNA nanotechnology 2. In the early ages of nucleic acid engineering, most manipulating approaches aimed to generate DNA‐based materials 3.…”

Supramolecular Wireframe DNA Polyhedra: Assembly and Applications

“…It is notable that 3D wireframe polyhedra based on RNA [89][90][91][92][93][94] and protein [95][96][97][98][99] have also appeared in recent literatures. In the case of in vivo applications, some fundamental issues need to be addressed for the polyhedral DNA structures: (1) how to build a more robust DNA polyhedron with increased in vivo circulation time; (2) how to target a specific tumor cell and a subcellular region with a DNA polyhedron, and (3) how to improve cellular uptake efficiency and facilitate lysosomal escape.…”