Functionally-interdependent shape-switching nanoparticles with controllable properties

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Halman, J., Khisamutdinov, E. F., Afonin, K. A., Satterwhite, E., Roark, B., Chandler, M., … Dobrovolskaia, M. A. (2017). Functionally-interdependent shape-switching nanoparticles with controllable properties. Nucleic Acids Research. https://doi.org/doi:10.1093/nar/gkx008
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Description

We introduce a new concept that utilizes cognate nucleic acid nanoparticles which are fully complementary and functionally-interdependent to each other. In the described approach, the physical interaction between sets of designed nanoparticles initiates a rapid isothermal shape change which triggers the activation of multiple functionalities and biological pathways including transcription, energy transfer, functional aptamers and RNA interference. The individual nanoparticles are not active and have controllable kinetics of re-association and fine-tunable chemical and thermodynamic stabilities. Computational algorithms were developed to accurately predict melting temperatures of nanoparticles of various compositions and trace the process of their re-association in silico. Additionally, tunable immunostimulatory properties of described nanoparticles suggest that the particles that do not induce pro-inflammatory cytokines and high levels of interferons can be used as scaffolds to carry therapeutic oligonucleotides, while particles with strong interferon and mild proinflammatory cytokine induction may qualify as vaccine adjuvants. The presented concept provides a simple, cost-effective and straightforward model for the development of combinatorial regulation of biological processes in nucleic acid nanotechnology.

Details
Title

Functionally-interdependent shape-switching nanoparticles with controllable properties

Author(s)

Halman, Justin
Khisamutdinov, Emil F.
Afonin, Kirill A.
Satterwhite, Emily
Roark, Brandon
Chandler, Morgan
Ivanina, Anna
Viard, Mathias
Bindewald, Eckart
Kasprzak, Wojciech K.
Panigaj, Martin
Bui, My N.
Lu, Jacob S.
Miller, Johann
Shapiro, Bruce A.
Dobrovolskaia, Marina A.

UNC Charlotte Affiliate Type

Graduate

Extent

1 online resource

Date Published

2017

Material Type

Journal article

Genre

articles

Resource Type

text

Abstract

We introduce a new concept that utilizes cognate nucleic acid nanoparticles which are fully complementary and functionally-interdependent to each other. In the described approach, the physical interaction between sets of designed nanoparticles initiates a rapid isothermal shape change which triggers the activation of multiple functionalities and biological pathways including transcription, energy transfer, functional aptamers and RNA interference. The individual nanoparticles are not active and have controllable kinetics of re-association and fine-tunable chemical and thermodynamic stabilities. Computational algorithms were developed to accurately predict melting temperatures of nanoparticles of various compositions and trace the process of their re-association in silico. Additionally, tunable immunostimulatory properties of described nanoparticles suggest that the particles that do not induce pro-inflammatory cytokines and high levels of interferons can be used as scaffolds to carry therapeutic oligonucleotides, while particles with strong interferon and mild proinflammatory cytokine induction may qualify as vaccine adjuvants. The presented concept provides a simple, cost-effective and straightforward model for the development of combinatorial regulation of biological processes in nucleic acid nanotechnology.

Subjects--Topics

Nucleic acids
Nanotechnology

Is Part Of

Nucleic acids research

Volume

Vol. 45, no. 4

Language

English

Published Version (Please cite this version)

doi:10.1093/nar/gkx008

Permalink

http://hdl.handle.net/20.500.13093/work:248

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