RNA Nanotechnology
We use crystal structures as a guide to design RNA and RNA-DNA hybrid nanostructures that self-assemble from small nucleic acid motifs and serve as combinatorial platforms for functionalization.
Design of a self-assembling RNA nano square:
(A) Secondary structure of the HCV IRES IIa-1 RNA.
(B) Crystal structure of the IIa-1 RNA.
(C) Secondary structure of the RNA square. The four copies of the IIa-1 core are highlighted in different colors. Lines indicate boundaries of oligonucleotides.
(D) Native polyacrylamide gel electrophoresis of IIa-1 and square RNA. The strong band in the lane containing both oligonucleotides ("inner" and "outer" strand) indicates formation of the RNA nano square.
Crystal structure of an RNA nano triangle
resolution: 2.60Å
method: molecular fragment replacement
R/Rfree: 0.19/0.24
space group: R32
PDB: 5CNR
Crystal structure-guided design of self-assembling RNA nanotriangles (2016) Boerneke MA, Dibrov SM & Hermann T. Angew. Chem. Int. Ed. 55, 4097-4100.
Programmed self-assembly of fluorescently labeled RNA squares:
(A) Four 5’-terminal bases in the oligonucleotides of the corner units constitute overlapping sequences for assembly via strand hybridization. In the crystallography construct, all four recognition sequences were identical (A), resulting in corners designated as A^A. Permutations were generated (B, C, D) for the programmed assembly of fluorescently labeled corners with non-identical recognition sequences (X^Y), which are unable to self-associate.
(B) Fluorescence of dye-labeled corners A^B-cy3 and C^D-cy5 in complementation experiments. A + symbol indicates the presence of a corner unit. Species that contribute to fluorescence in each experiment are depicted at the bottom.
RNA nano architectures as self-assembling combinatorial platforms
Versatile kit of robust nanoshapes self-assembling from RNA and DNA modules:
RNA-DNA hybrid nanoshapes integrate RNA motifs as architectural joints and DNA building blocks as functional modules. The partitioning of architectural and functional roles for RNA and DNA modules in the hybrid nanoshapes is a novel approach that provides a prototype for expanding chemical diversity and functionality of self-assembling nucleic acid nanomaterials for applications in molecular recognition, sensor and catalyst development as well as protein interaction studies.
Versatile kit of robust nanoshapes self-assembling from RNA and DNA modules (2019) Monferrer A, Zhang D, Lushnikov AJ & Hermann T. Nature Communications 10, 608.
RNA-DNA hybrid nano-architectures