Rational design of DNA nanostructures for disease diagnostics and prognostics
File(s)
Author(s)
Smith, Francesca
Type
Thesis
Abstract
Strand displacement is a critical nucleic acid reaction that underlies most dynamic nucleic acid circuits or reaction networks. The kinetic and thermodynamic properties of DNA-based strand displacement reactions have been extensively characterised, both experimentally and computationally. This critical work has revealed general design principles that enable construction de novo reaction schemes with novel complexity, while maintaining predictable reaction kinetics.
Despite the importance of DNA as a fundamental building material in nucleic acid nanotechnology, recent years have seen increased interest in exploiting RNA within nucleic acid devices. The distinct structural and catalytic properties of RNA have the potential to unlock novel functionality within nanoscale technologies. Further, the critical intracellular functions of RNA, including protein coding and gene expression regulation, make aberrant RNA signatures informative biomarkers in disease diagnosis and prognosis. Overall, the fundamental role of RNA in biological processes motivates the development of hybrid nucleic acid nanotechnologies that effectively interface with such processes to manipulate or monitor biological systems. Nonetheless, there is still a limited understanding of RNA/DNA hybrid strand displacement kinetics, with as yet no systematic characterisation, limiting design of novel RNA/DNA hybrid reaction schemes with tightly regulated dynamics.
Herein a systematic characterisation of RNA/DNA strand displacement is performed across a range of common design parameters. Leveraging base pair level models to interpret the data, a strong sequence dependence is revealed for RNA/DNA strand displacement that is not observed for the equivalent DNA system...
Despite the importance of DNA as a fundamental building material in nucleic acid nanotechnology, recent years have seen increased interest in exploiting RNA within nucleic acid devices. The distinct structural and catalytic properties of RNA have the potential to unlock novel functionality within nanoscale technologies. Further, the critical intracellular functions of RNA, including protein coding and gene expression regulation, make aberrant RNA signatures informative biomarkers in disease diagnosis and prognosis. Overall, the fundamental role of RNA in biological processes motivates the development of hybrid nucleic acid nanotechnologies that effectively interface with such processes to manipulate or monitor biological systems. Nonetheless, there is still a limited understanding of RNA/DNA hybrid strand displacement kinetics, with as yet no systematic characterisation, limiting design of novel RNA/DNA hybrid reaction schemes with tightly regulated dynamics.
Herein a systematic characterisation of RNA/DNA strand displacement is performed across a range of common design parameters. Leveraging base pair level models to interpret the data, a strong sequence dependence is revealed for RNA/DNA strand displacement that is not observed for the equivalent DNA system...
Version
Open Access
Date Issued
2024-01-01
Date Awarded
2024-04-15
Copyright Statement
Creative Commons Attribution Licence
License URL
Advisor
Stevens, Molly
Ouldridge, Thomas
Sponsor
Engineering and Physical Sciences Research Council
Grant Number
EP/S022856/1
Publisher Department
Materials
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)