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dc.contributor.advisorShih, William M
dc.contributor.authorMinev, Dionis
dc.date.accessioned2021-08-04T05:01:33Z
dc.date.created2020
dc.date.issued2020-10-06
dc.date.submitted2020-11
dc.identifier.citationMinev, Dionis. 2020. Kinetic control of DNA self-assembly with programmable monomer coordination. Doctoral dissertation, Harvard University Graduate School of Arts and Sciences.
dc.identifier.other28150970
dc.identifier.urihttps://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37368965*
dc.description.abstractBiological systems exhibit remarkable control over the assembly of complex multi-component molecular architectures across several orders of magnitude in size, in which biomolecules are primarily connected by reversible, noncovalent interactions. These weak, albeit strictly coordinated, interactions are governed by the molecular accountancy of energetic credits and debits. This feature permits biomolecular assemblies to gain kinetic control over spontaneous nucleation. Achieving programmable control over nucleation is likewise a highly desirable attribute in synthetic self-assembly systems. To date, the field of DNA nanotechnology offers an unrivaled programmability of synthetic biomolecular assemblies due to established structural motifs and the self-recognition of complementary single-stranded DNA. In the past decades, DNA self-assembly systems have implemented kinetically-controlled architectures and developed complex nucleic acid nanoconstructions and computations. However, control over spontaneous nucleation remains limited in existing DNA assemblies to near-reversible, slow growth conditions. This is a problem that ultimately restricts the progression of important applications, including all-or-nothing assembly of microscale structures with nanoscale features, ultrasensitive bioanalyte detection, and robust algorithmic assembly. Moreover, practical limitations in implementing DNA nanostructure designs arise from the length restrictions of synthetic DNA or the cumbersome enzymatic production of DNA with low yields. To address these challenges, I present the collaborative work in this dissertation in two parts. First, I demonstrate the programmable nucleation of synthetic supramolecular DNA structures termed crisscross assembly. This work establishes a theoretical analysis and experimental validation of the all-or-nothing assembly of multi-micrometer structures built from highly coordinated single-stranded DNA monomers. The monomers polymerize in a seed-dependent fashion and maintain this behavior under irreversible reaction conditions. In the second part of this dissertation, I present an in vitro method for the rapid enzymatic production of single-stranded DNA and its application in DNA nanotechnology, biological imaging, and gene editing.
dc.format.mimetypeapplication/pdf
dc.language.isoen
dash.licenseLAA
dc.subjectDNA nanotechnology
dc.subjectDNA self-assembly
dc.subjectLiving supramolecular polymerization
dc.subjectSingle-stranded DNA synthesis
dc.subjectBioengineering
dc.subjectBiophysics
dc.titleKinetic control of DNA self-assembly with programmable monomer coordination
dc.typeThesis or Dissertation
dash.depositing.authorMinev, Dionis
dc.date.available2021-08-04T05:01:33Z
thesis.degree.date2020
thesis.degree.grantorHarvard University Graduate School of Arts and Sciences
thesis.degree.levelDoctoral
thesis.degree.namePh.D.
dc.contributor.committeeMemberManoharan, Vinothan N
dc.contributor.committeeMemberWong, Wesley P
dc.contributor.committeeMemberNeedleman, Daniel J
dc.type.materialtext
thesis.degree.departmentEngineering and Applied Sciences - Engineering Sciences
dc.identifier.orcid0000-0002-7846-8872
dash.author.emaildio.minev@gmail.com


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