Dirks, Robert Michael (2005) Analysis, design, and construction of nucleic acid devices. Dissertation (Ph.D.), California Institute of Technology. http://resolver.caltech.edu/CaltechETD:etd-05242005-133116
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|
|Thesis Availability:||Public (worldwide access)|
|Defense Date:||11 May 2005|
|Default Usage Policy:||No commercial reproduction, distribution, display or performance rights in this work are provided.|
|Deposited By:||Imported from ETD-db|
|Deposited On:||26 May 2005|
|Last Modified:||22 Aug 2016 21:15|
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