Journal Home > Volume 14 , Issue 1
Nano Research 2021, 14(1): 46-51 https://doi.org/10.1007/s12274-020-3008-1
Research Article | Issue | Published: 05 January 2021

Complex RNA-DNA hybrid nanoshapes from iterative mix-and-match screening

Show Author's Information Shi Chen3,  Zhiyuan Zhang1,  Eugene Alforque1,  Thomas Hermann1,2( )
Department of Chemistry and Biochemistry, University of California, San Diego, CA 92093, USA
Center for Drug Discovery Innovation, University of California, San Diego, CA 92093, USA
Materials Science and Engineering Program, University of California, San Diego, CA 92093, USA
Keywords:
nucleic acid nanotechnology, nanoshapes, ribonucleic acid (RNA) three-way junction (3WJ), RNA, deoxyribonucleic acid (DNA), sub-10 nm features
Topics:
Atomic force microscopyBiomolecules DNA RNA
Cite this article:
Chen S, Zhang Z, Alforque E, et al. Complex RNA-DNA hybrid nanoshapes from iterative mix-and-match screening. Nano Research, 2021, 14(1): 46-51. https://doi.org/10.1007/s12274-020-3008-1
Download citation
EndNote(RIS)
BibTeX

552

Views

31

Downloads

Citations

5

Crossref

0

WoS

5

Scopus

1

CSCD

Abstract Full text Electronic supplementary material About this article

Hybrid nucleic acid nanostructures partition architectural and functional roles between ribonucleic acid (RNA) joints and deoxyribonucleic acid (DNA) connectors. Nanoshapes self-assemble from nucleic acid modules through synergistic stabilization of marginally stable base pairing interactions within circularly closed polygons. Herein, we report the development of hybrid nanoshapes that include multiple different RNA modules such as internal loop and three-way junction (3WJ) motifs. An iterative mix-and-match screening approach was used to identify suitable DNA connectors that furnished stable nanoshapes for combinations of different RNA modules. The resulting complex multicomponent RNA-DNA hybrid nanoshapes were characterized by atomic force microscopy (AFM) imaging. Our research provides proof of concept for modular design, assembly and screening of RNA-DNA hybrid nanoshapes as building blocks for complex extended nucleic acid materials with features at the sub-10 nm scale.


menu
Abstract
Full text
Outline
Electronic supplementary material
About this article

Complex RNA-DNA hybrid nanoshapes from iterative mix-and-match screening

Show Author's information Shi Chen3, Zhiyuan Zhang1, Eugene Alforque1, Thomas Hermann1,2( )
Department of Chemistry and Biochemistry, University of California, San Diego, CA 92093, USA
Center for Drug Discovery Innovation, University of California, San Diego, CA 92093, USA
Materials Science and Engineering Program, University of California, San Diego, CA 92093, USA

Abstract

Hybrid nucleic acid nanostructures partition architectural and functional roles between ribonucleic acid (RNA) joints and deoxyribonucleic acid (DNA) connectors. Nanoshapes self-assemble from nucleic acid modules through synergistic stabilization of marginally stable base pairing interactions within circularly closed polygons. Herein, we report the development of hybrid nanoshapes that include multiple different RNA modules such as internal loop and three-way junction (3WJ) motifs. An iterative mix-and-match screening approach was used to identify suitable DNA connectors that furnished stable nanoshapes for combinations of different RNA modules. The resulting complex multicomponent RNA-DNA hybrid nanoshapes were characterized by atomic force microscopy (AFM) imaging. Our research provides proof of concept for modular design, assembly and screening of RNA-DNA hybrid nanoshapes as building blocks for complex extended nucleic acid materials with features at the sub-10 nm scale.

Keywords: nucleic acid nanotechnology, nanoshapes, ribonucleic acid (RNA) three-way junction (3WJ), RNA, deoxyribonucleic acid (DNA), sub-10 nm features

References(30)

[1]
N. C. Seeman,; H. F. Sleiman, DNA nanotechnology. Nat. Rev. Mater. 2017, 3, 17068.
Google Scholar
[2]
L. Jaeger,; A. Chworos, The architectonics of programmable RNA and DNA nanostructures. Curr. Opin. Struct. Biol. 2006, 16, 531-543.
Google Scholar
[3]
D. Jasinski,; F. Haque,; D. W. Binzel,; P. X. Guo, Advancement of the emerging field of RNA nanotechnology. ACS Nano 2017, 11, 1142-1164.
Google Scholar
[4]
C. Geary,; P. W. K. Rothemund,; E. S. Andersen, A single-stranded architecture for cotranscriptional folding of RNA nanostructures. Science 2014, 345, 799-804.
Google Scholar
[5]
K. A. Afonin,; M. Viard,; A. N. Martins,; S. J. Lockett,; A. E. Maciag,; E. O. Freed,; E. Heldman,; L. Jaeger,; R. Blumenthal,; B. A. Shapiro, Activation of different split functionalities on re-association of RNA-DNA hybrids. Nat. Nanotechnol. 2013, 8, 296-304.
Google Scholar
[6]
K. A. Afonin,; R. Desai,; M. Viard,; M. L. Kireeva,; E. Bindewald,; C. L. Case,; A. E. Maciag,; W. K. Kasprzak,; T. Kim,; A. Sappe, et al. Co-transcriptional production of RNA-DNA hybrids for simultaneous release of multiple split functionalities. Nucleic Acids Res. 2014, 42, 2085-2097.
Google Scholar
[7]
S. Agarwal,; E. Franco, Enzyme-driven assembly and disassembly of hybrid DNA-RNA nanotubes. J. Am. Chem. Soc. 2019, 141, 7831-7841.
Google Scholar
[8]
W. N. Ke,; E. P. Hong,; R. F. Saito,; M. C. Rangel,; J. Wang,; M. Viard,; M. Richardson,; E. F. Khisamutdinov,; M. Panigaj,; N. V. Dokholyan, et al. RNA-DNA fibers and polygons with controlled immunorecognition activate RNAi, FRET and transcriptional regulation of NF-κB in human cells. Nucleic Acids Res. 2019, 47, 1350-1361.
Google Scholar
[9]
K. A. Afonin,; M. Viard,; I. Kagiampakis,; C. L. Case,; M. A. Dobrovolskaia,; J. Hofmann,; A. Vrzak,; M. Kireeva,; W. K. Kasprzak,; V. N. KewalRamani, et al. Triggering of RNA interference with RNA-RNA, RNA-DNA, and DNA-RNA nanoparticles. ACS Nano 2015, 9, 251-259.
Google Scholar
[10]
A. Monferrer,; D. Zhang,; A. J. Lushnikov,; T. Hermann, Versatile kit of robust nanoshapes self-assembling from RNA and DNA modules. Nat. Commun. 2019, 10, 608.
Google Scholar
[11]
S. Chen,; T. Hermann, RNA-DNA hybrid nanoshapes that self-assemble dependent on ligand binding. Nanoscale 2020, 12, 3302-3307.
Google Scholar
[12]
B. Yurke,; A. J. Turberfield,; A. P., Mills, Jr.; F. C. Simmel,; J. L. Neumann, A DNA-fuelled molecular machine made of DNA. Nature 2000, 406, 605-608.
Google Scholar
[13]
P. X. Guo,; C. L. Zhang,; C. P. Chen,; K. Garver,; M. Trottier, Inter-RNA interaction of phage φ29 pRNA to form a hexameric complex for viral DNA transportation. Mol. Cell 1998, 2, 149-155.
Google Scholar
[14]
D. Shu,; Y. Shu,; F. Haque,; S. Abdelmawla,; P. X. Guo, Thermodynamically stable RNA three-way junction for constructing multifunctional nanoparticles for delivery of therapeutics. Nat. Nanotechnol. 2011, 6, 658-667.
Google Scholar
[15]
Y. Shu,; F. Haque,; D. Shu,; W. Li,; Z. Q. Zhu,; M. Kotb,; Y. Lyubchenko,; P. X. Guo, Fabrication of 14 different RNA nanoparticles for specific tumor targeting without accumulation in normal organs. RNA 2013, 19, 767-777.
Google Scholar
[16]
E. F. Khisamutdinov,; D. L. Jasinski,; H. Li,; K. M. Zhang,; W. Chiu,; P. X. Guo, Fabrication of RNA 3D nanoprisms for loading and protection of small RNAs and model drugs. Adv. Mater. 2016, 28, 10079-10087.
Google Scholar
[17]
E. F. Khisamutdinov,; H. Li,; D. L. Jasinski,; J. Chen,; J. Fu,; P. X. Guo, Enhancing immunomodulation on innate immunity by shape transition among RNA triangle, square and pentagon nanovehicles. Nucleic Acids Res. 2014, 42, 9996-10004.
Google Scholar
[18]
H. Li,; K. M. Zhang,; F. M. Pi,; S. J. Guo,; L. Shlyakhtenko,; W. Chiu,; D. Shu,; P. X. Guo, Controllable self-assembly of RNA tetrahedrons with precise shape and size for cancer targeting. Adv. Mater. 2016, 28, 7501-7507.
Google Scholar
[19]
C. H. Hao,; X. Li,; C. Tian,; W. Jiang,; G. S. Wang,; C. D. Mao, Construction of RNA nanocages by re-engineering the packaging RNA of Phi29 bacteriophage. Nat. Commun. 2014, 5, 3890.
Google Scholar
[20]
M. Schwarz-Schilling,; A. Dupin,; F. Chizzolini,; S. Krishnan,; S. S. Mansy,; F. C. Simmel, Optimized assembly of a multifunctional RNA-protein nanostructure in a cell-free gene expression system. Nano Lett. 2018, 18, 2650-2657.
Google Scholar
[21]
A. C. Hill,; L. E. Bartley,; S. J. Schroeder, Prohead RNA: A noncoding viral RNA of novel structure and function. WIREs RNA 2016, 7, 428-437.
Google Scholar
[22]
F. Xiao,; B. Demeler,; P. X. Guo, Assembly mechanism of the sixty-subunit nanoparticles via interaction of RNA with the reengineered protein connector of phi29 DNA-packaging motor. ACS Nano 2010, 4, 3293-3301.
Google Scholar
[23]
C. C. Xu,; H. Li,; K. M. Zhang,; D. W. Binzel,; H. R. Yin,; W. Chiu,; P. X. Guo, Photo-controlled release of paclitaxel and model drugs from RNA pyramids. Nano Res. 2019, 12, 41-48.
Google Scholar
[24]
E. F. Khisamutdinov,; D. L. Jasinski,; P. X. Guo, RNA as a boiling-resistant anionic polymer material to build robust structures with defined shape and stoichiometry. ACS Nano 2014, 8, 4771-4781.
Google Scholar
[25]
L. Parlea,; E. Bindewald,; R. Sharan,; N. Bartlett,; D. Moriarty,; J. Oliver,; K. A. Afonin,; B. A. Shapiro, Ring Catalog: A resource for designing self-assembling RNA nanostructures. Methods 2016, 103, 128-137.
Google Scholar
[26]
W. K. Kasprzak,; N. A. Ahmed,; B. A. Shapiro, Modeling ligand docking to RNA in the design of RNA-based nanostructures. Curr. Opin. Biotechnol. 2020, 63, 16-25.
Google Scholar
[27]
K. A. Afonin,; E. Bindewald,; A. J. Yaghoubian,; N. Voss,; E. Jacovetty,; B. A. Shapiro,; L. Jaeger, In vitro assembly of cubic RNA-based scaffolds designed in silico. Nat. Nanotechnol. 2010, 5, 676-682.
Google Scholar
[28]
P. W. K. Rothemund, Folding DNA to create nanoscale shapes and patterns. Nature 2006, 440, 297-302.
Google Scholar
[29]
G. Vantomme,; E. W. Meijer, The construction of supramolecular systems. Science 2019, 363, 1396-1397.
Google Scholar
[30]
L. S. Shlyakhtenko,; A. A. Gall,; A. Filonov,; Z. Cerovac,; A. Lushnikov,; Y. L. Lyubchenko, Silatrane-based surface chemistry for immobilization of DNA, protein-DNA complexes and other biological materials. Ultramicroscopy 2003, 97, 279-287.
Google Scholar
File
12274_2020_3008_MOESM1_ESM.pdf (1.3 MB)
Publication history
Copyright
Acknowledgements

Publication history

Received: 06 June 2020
Revised: 22 July 2020
Accepted: 26 July 2020
Published: 05 January 2021
Issue date: January 2021

Copyright

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature

Acknowledgements

This work was supported by the National Science Foundation, Chemical Measurement & Imaging Program, grant number CHE CMI 1608287. We thank A. J. Lushnikov for helping with AFM imaging.

Return