Skip to content
BY-NC-ND 4.0 license Open Access Published by De Gruyter Open Access September 23, 2017

Activation of Multiple Functionalities Through Interacting Nanoparticles

Morgan Chandler , Justin R. Halman and Emil F. Khisamutdinov EMAIL logo


Nucleic acids are biocompatible, robust, and highly versatile polymers that can be used to design fine-tunable and dynamically responsive nanostructures. In this report, we focus our attention to recently introduced concepts of interdependent, cognate nucleic acid nanoparticles assembly that take advantage of dynamic interactions and consequent shape-switching to trigger the activation of multiple functionalities. Particularly, we discuss re-association of thermodynamically driven complementary nanocubes (“cube” and complementary “anti-cube”) into functional duplexes that do not require toehold interactions or extensive computational design, bringing a new perspective for utility of nucleic acid nanoparticles as a drug carriers, biosensors, and templates for the formation of siRNA duplexes.


[1] Afonin, K. A.; Bindewald, E.; Yaghoubian, A. J.; Voss, N.; Jacovetty, E.; Shapiro, B. A.; Jaeger, L., In vitro assembly of cubic RNA-based scaffolds designed in silico. Nat Nanotechnol 2010, 5 (9), 676-82.10.1038/nnano.2010.160Search in Google Scholar PubMed PubMed Central

[2] Guo, P., The emerging field of RNA nanotechnology. Nat Nanotechnol 2010, 5 (12), 833-42.10.1038/nnano.2010.231Search in Google Scholar PubMed PubMed Central

[3] Haque, F.; Shu, D.; Shu, Y.; Shlyakhtenko, L. S.; Rychahou, P. G.; Evers, B. M.; Guo, P., Ultrastable synergistic tetravalent RNA nanoparticles for targeting to cancers. Nano Today 2012, 7 (4), 245-257.10.1016/j.nantod.2012.06.010Search in Google Scholar PubMed PubMed Central

[4] Geary, C.; Rothemund, P. W.; Andersen, E. S., RNA nanostructures. A single-stranded architecture for cotranscriptional folding of RNA nanostructures. Science 2014, 345 (6198), 799-804.Search in Google Scholar

[5] Pinheiro, A. V.; Han, D.; Shih, W. M.; Yan, H., Challenges and opportunities for structural DNA nanotechnology. Nat Nanotechnol 2011, 6 (12), 763-72.10.1038/nnano.2011.187Search in Google Scholar PubMed PubMed Central

[6] Bindewald, E.; Afonin, K. A.; Viard, M.; Zakrevsky, P.; Kim, T.; Shapiro, B. A., Multistrand Structure Prediction of Nucleic Acid Assemblies and Design of RNA Switches. Nano Lett 2016, 16 (3), 1726-35.10.1021/acs.nanolett.5b04651Search in Google Scholar PubMed PubMed Central

[7] Afonin, K. A.; Viard, M.; Martins, A. N.; Lockett, S. J.; Maciag, A. E.; Freed, E. O.; Heldman, E.; Jaeger, L.; Blumenthal, R.; Shapiro, B. A., Activation of different split functionalities on re-association of RNA-DNA hybrids. Nat Nanotechnol 2013, 8 (4), 296-304.10.1038/nnano.2013.44Search in Google Scholar PubMed PubMed Central

[8] Afonin, K. A.; Viard, M.; Tedbury, P.; Bindewald, E.; Parlea, L.; Howington, M.; Valdman, M.; Johns-Boehme, A.; Brainerd, C.; Freed, E. O.; Shapiro, B. A., The Use of Minimal RNA Toeholds to Trigger the Activation of Multiple Functionalities. Nano Lett 2016, 16 (3), 1746-53.10.1021/acs.nanolett.5b04676Search in Google Scholar PubMed PubMed Central

[9] Groves, B.; Chen, Y. J.; Zurla, C.; Pochekailov, S.; Kirschman, J. L.; Santangelo, P. J.; Seelig, G., Computing in mammalian cells with nucleic acid strand exchange. Nat Nanotechnol 2016, 11 (3), 287-94.10.1038/nnano.2015.278Search in Google Scholar PubMed PubMed Central

[10] Rogers, T. A.; Andrews, G. E.; Jaeger, L.; Grabow, W. W., Fluorescent monitoring of RNA assembly and processing using the split-spinach aptamer. ACS Synth Biol 2015, 4 (2), 162-6.10.1021/sb5000725Search in Google Scholar PubMed

[11] Halman, J. R.; Satterwhite, E.; Roark, B.; Chandler, M.; Viard, M.; Ivanina, A.; Bindewald, E.; Kasprzak, W. K.; Panigaj, M.; Bui, M. N.; Lu, J. S.; Miller, J.; Khisamutdinov, E. F.; Shapiro, B. A.; Dobrovolskaia, M. A.; Afonin, K. A., Functionally-interdependent shape-switching nanoparticles with controllable properties. Nucleic Acids Res 2017. 10.1093/nar/gkx008Search in Google Scholar PubMed PubMed Central

[12] Dobrovolskaia, M. A.; McNeil, S. E., Immunological and hematological toxicities challenging clinical translation of nucleic acid-based therapeutics. Expert Opin Biol Ther 2015, 15 (7), 1023-48.10.1517/14712598.2015.1014794Search in Google Scholar PubMed

[13] Blanco, P.; Palucka, A. K.; Pascual, V.; Banchereau, J., Dendritic cells and cytokines in human inflammatory and autoimmune diseases. Cytokine Growth Factor Rev 2008, 19 (1), 41-52.10.1016/j.cytogfr.2007.10.004Search in Google Scholar PubMed PubMed Central

[14] Filonov, G. S.; Moon, J. D.; Svensen, N.; Jaffrey, S. R., Broccoli: rapid selection of an RNA mimic of green fluorescent protein by fluorescence-based selection and directed evolution. J Am Chem Soc 2014, 136 (46), 16299-308.10.1021/ja508478xSearch in Google Scholar PubMed PubMed Central

[15] Reagan-Shaw, S.; Ahmad, N., Silencing of polo-like kinase (Plk) 1 via siRNA causes induction of apoptosis and impairment of mitosis machinery in human prostate cancer cells: implications for the treatment of prostate cancer. FASEB J 2005, 19 (6), 611-3.10.1096/fj.04-2910fjeSearch in Google Scholar PubMed

[16] Ruckert, F.; Samm, N.; Lehner, A. K.; Saeger, H. D.; Grutzmann, R.; Pilarsky, C., Simultaneous gene silencing of Bcl-2, XIAP and Survivin re-sensitizes pancreatic cancer cells towards apoptosis. BMC Cancer 2010, 10, 37910.1186/1471-2407-10-379Search in Google Scholar PubMed PubMed Central

Received: 2017-5-3
Accepted: 2017-5-31
Published Online: 2017-9-23
Published in Print: 2017-9-26

© 2017

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 License.

Downloaded on 8.12.2022 from
Scroll Up Arrow