Due to their biocompatibility and parallel data processing, DNA computational devices are highly desired for applications in diagnosis and treatment of cancer, infectious and genetic diseases. Much like in modern electronic devices, DNA computation is based on the logic gates - by directly interacting with DNA or RNA input molecules, they produce a specific output depending on their embedded logic function. This work is devoted to the development of functional parts of a future DNA nanorobot for biomedical applications. Specifically, we used DNA nanotechnology and the concept of multicomponent DNA probes to develop three parts of the DNA nanorobot: computing, actuating, and sensing. The computation function was addressed by developing construct with two integrated NAND gates, capable of processing three different DNA or RNA inputs. The second "smart" construct produces actuating function – cleavage of RNA for housekeeping gene in response to recognition of RNA inputs, generated by cancer cells. The third construct is an original DNA "Cephalopod-tile", with improved sensing function, capable of recognizing highly structured biological analytes, such as 16S rRNA of E.coli, as well as increasing hybridization kinetics with targets up to 465 times. These nanoconstructs contributed to development of original DNA nanomachine with OR logic function for treatment of cancer. Theses for Defense 1. Computing: It is possible to design tile-associated DNA NAND logic gates that can be integrated in communicating circuits. 2. Actuating: It is possible to create a DNA nano-construction that can cut out a marker fragment from a longer RNA sequence and use it as an activator for triggering cleavage of another RNA sequence. 3. Sensing: A DNA probe equipped with analyte capture function can increase hybridization rates between DNA and RNA analytes. 4. Sensing, computation, and actuating: It is possible to design multifunctional DNA nanomachines with sensing, computation, and therapeutic modules.
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Doctor of Philosophy (Ph.D.)
College of Sciences
Length of Campus-only Access
Doctoral Dissertation (Open Access)
Molden, Tatiana, "From DNA Logic Gates to DNA Nanorobots" (2022). Electronic Theses and Dissertations, 2020-. 1259.