Advances in DNA technology towards dynamic assemblies and biological applications

Wong, Ngo Yin

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Description

Title

Advances in DNA technology towards dynamic assemblies and biological applications

Author(s)

Wong, Ngo Yin

Issue Date

2013-05-24T22:18:07Z

Director of Research (if dissertation) or Advisor (if thesis)

Lu, Yi

Doctoral Committee Chair(s)

Lu, Yi

Committee Member(s)

• Braun, Paul V.
• Cheng, Jianjun
• Granick, Steve

Department of Study

Materials Science & Engineerng

Discipline

Materials Science & Engr

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• Deoxyribonucleic Acid (DNA)
• Nanotechnology
• Scaffolding
• in vitro uptake
• aptamers

Abstract

One of the major research aims in Materials Science and Engineering for the past two decades has pertained to the development of capabilities to manipulate and characterize materials on the molecular and atomic level. This capability has been largely driven by technological and engineering advances in the semiconducting industry, where better controls and higher resolution equates to better device performance and higher profits. Inspired by such lithographic approaches, there has been a parallel push to drive bottom up, self-assembly techniques, where short and long range forces drive the assembly of nanoscale components assemble into hundreds of billions of complexes and devices simultaneously. Correspondingly, our ability to form high quality and increasingly complex structures based on the principles of self-assembly demands the development of a highly repeatable, robust, and well characterized system. While the concepts of self-assembly is simple, the realization of high quality nanoscale assembly remains a stubbornly difficult challenge due a fundamental trade-off between degree of control, throughput (yield) of the assembly, and complexity of the final assembly. In the early 1980’s, Professor Nadrian Seeman published his seminal work on the design of DNA tiles, which along with his group, became the field now known as structural DNA nanotechnology. Professor Chad Mirkin and several others then later realized the power of complementary DNA can be utilized as a “smart glue” to programmably assembly many different types of nanomaterials. In the following three decades, DNA based nanotechnology has advanced greatly due to the commercial availability of artificially synthesized oligonucleotides, a vast library of chemical and enzymatic modifications, and the work of hundreds of groups around the world. This thesis will describe efforts made to advance the field by identifying new conjugation chemistries that enable two and three dimensional scaffolding of nanomaterials on complex DNA structures. Another extraordinary property of DNA was first described by Larry Gold and Jack Szostak and has since evolved into what is now functional DNA (f-DNA). The role of proteins (peptide chains) and ribozymes (RNA molecules) in a litany of biological enzymatic functions have long been studied. Functional DNA follows the hypothesis that certain DNA sequences will exhibit catalytic activity (much like ribozymes and proteins) or target recognition (much like antibodies). Of particular interest to the current thesis is functional DNA that has targeting properties based on their three dimensional structure in solution, also common known as DNA aptamers. Aptamers are selected through a process known as Systematic Evolution of Ligands by Exponential Enrichment or SELEX. DNA aptamers have drawn a great deal of attention as the next generation antibody due to (1) lower development and production cost, (2) higher stability, (3) more simple to characterize and modify. With a growing library of aptamers with target specific interactions, some of the most exiting research is the development of next generation medical imaging and therapies based on aptamer functionalities, in combination with novel nanomaterials. In this thesis, we describe work introducing a new type of optically active nanoparticles, that exhibits useful properties for disease diagnosis and therapy while reducing unwanted side effects. As the rest of the thesis will demonstrate in great detail, the future of DNA based nanotechnologies is tremendous, with the potential to impact electronics, optics, and medical devices of the future.

Graduation Semester

2013-05

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Copyright 2013 Ngo Yin Wong

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