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Analysis, Design, and Construction of Nucleic Acid Devices


Dirks, Robert Michael (2005) Analysis, Design, and Construction of Nucleic Acid Devices. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/VZ43-FM66.


Nucleic acids present great promise as building blocks for nanoscale devices. To achieve this potential, methods for the analysis and design of DNA and RNA need to be improved. In this thesis, traditional algorithms for analyzing nucleic acids at equilibrium are extended to handle a class of pseudoknots, with examples provided relevant to biologists and bioengineers. With these analytical tools in hand, nucleic acid sequences are designed to maximize the equilibrium probability of a desired fold. Upon analysis, it is concluded that both affinity and specificity are important when choosing a sequence; this conclusion holds for a wide range of target structures and is robust to random perturbations to the energy model. Applying the intuition gained from these studies, a process called hybridization chain reaction (HCR) is invented, and sequences are chosen that experimentally verify this phenomenon. In HCR, a small number of DNA or RNA molecules trigger a system wide configurational change, allowing the amplification and detection of specific, nucleic acid sequences. As an extension, HCR is combined with a pre-existing aptamer domain to successfully construct an ATP sensor, and the groundwork is laid for the future development of sensors for other small molecules. In addition, recent studies on multi-stranded algorithms and improvements to HCR are included in the appendices. Not only will these advancements increase our understanding of biological RNAs, but they will also provide valuable tools for the future development of nucleic acid nanotechnologies.

Item Type:Thesis (Dissertation (Ph.D.))
Subject Keywords:Design; DNA; HCR; Hybridization Chain Reaction; Nucleic acids; Pseudoknots; RNA
Degree Grantor:California Institute of Technology
Division:Chemistry and Chemical Engineering
Major Option:Chemistry
Thesis Availability:Public (worldwide access)
Research Advisor(s):
  • Pierce, Niles A.
Thesis Committee:
  • Mayo, Stephen L. (chair)
  • Lewis, Nathan Saul
  • Pierce, Niles A.
  • Goddard, William A., III
Defense Date:11 May 2005
Record Number:CaltechETD:etd-05242005-133116
Persistent URL:
Default Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:1998
Deposited By: Imported from ETD-db
Deposited On:26 May 2005
Last Modified:08 Nov 2023 00:43

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